In the mid-eighteenth century Manchester was a rapidly developing industrial centre. In 1745, Liverpool founded an Infirmary prompting Manchester to follow. Manchester Infirmary was founded in 1752 by a group of men, led by Joseph Bancroft and the surgeon Charles White, in a small house with about twelve beds on Garden Street (off Withy Grove). Patients were admitted on the recommendation of subscribers, in a system of patronage designed to raise money for the hospital and ensure patients were worthy objects of the charity. It was a regional rather than urban charity, with subscribers from east Lancashire and Cheshire as well as Manchester. From the start the Infirmary was under pressure to admit more patients and the adjoining house was acquired to provide more facilities in 1753. Further expansion arrived with the opening of the new Infirmary in 1755. It had fifty beds and a second wing of the same size was built within a year. The new Infirmary was built on land known as Daub-holes, which today is known as Piccadilly, and included a pond. In 1779, in an attempt to increase subscriptions, the Infirmary built a set of baths, with special rates for trustees. These baths proved extremely popular with trustees and other members of the public who paid a fee. In the early days the Infirmary also engaged in a small-pox innoculation programme. The Infirmary did not admit pregnant women, children, lunatics or sufferers from infectious diseases. These exclusions led to the development of specialised voluntary hospitals, many closely associated with MRI. The Manchester Lunatic Hospital, which later became Cheadle Royal Hospital opened next to the Infirmary in 1766, and was managed by the Infirmary Board. More controversial was the founding in 1790 of the Lying-in Hospital, now known as St Mary's. Charles White and three other surgeons resigned from the Infirmary in order to found the Lying-in Hospital and the loss of Charles White was a great blow to the Infirmary.
By the late eighteenth century MRI had became highly politicised. This was partly due to the development of politics and a political class in Manchester (which included many medical men) but also related to the recurrence of fever and hunger in the cotton towns. This politicisation is evident in the ongoing campaign of the radical Whigs to enlarge the Infirmary. The honorary surgeons and physicians resigned in an attempt to block reform but the reformers won and the MRI entered a phase of rapid development. Uniquely in England, a Dispensary service was built on the existing work of the Infirmary rather than independently. In 1781 a home patient service was begun for patients with infectious diseases who could not be admitted to the hospital; this proved to be a very successful service. The hospital became officially known as the Infirmary, Dispensary, Lunatic Hospital and Asylum in Manchester. The expansion was popular and MRI became a nationally significant hospital, thanks to the unique strength of dissenters in Manchester. In 1793 the Infirmary began offering teaching for medical students, who had usually completed an apprenticeship. In 1795 Dr John Ferriar, one of the physicians at the MRI, led the formation of the Board of Health. The Board of Health saw that the wards that the Infirmary set aside for fever cases were insufficient, and founded the House of Recovery. The Infirmary thus associated itself with the very beginnings of a public health service in Manchester.
By the 1800s, Manchester was rapidly increasing in size, a growth that brought with it problems of great poverty and also conservatism among the middle classes. MRI became again the focus of local politics when its treatment of victims of the Peterloo Massacre of 1819 was the subject of much speculation. The out-patients service grew very rapidly and MRI was often full. However, lack of funds and disputes between trustees and medical men delayed the expansion of the Infirmary. There were some developments however, and by 1828 the building had been extended to include a reception room for accidents and better accommodation. The Infirmary received Royal Patronage in 1830 and became Manchester Royal Infirmary. MRI was substantially rebuilt in 1840s and 1850s. This rebuilding was made possible by the movement of Manchester Lunatic Hospital to Cheadle, and the closure of the House of Recovery in 1855. The rebuilding of the Infirmary was closely linked with the civic improvement schemes of the time. The new building had 275 general beds and 35 fever beds. However, it was not a massive expansion, staff accommodation still did not meet the standards of the 1848 Health Act. By 1850s, more than half of the deaths which occurred at the hospital were the result of accidents. This high proportion was probably unique and was largely a result of Manchester Industry. Conditions at MRI were poor, infections were rife, and mortality figures reached a high in 1860. There were arguments for moving MRI out of the city centre, but these met opposition. A compromise was reached with a plan of rural convalescent hospitals working in conjunction with city centre hospital. This plan was strengthened by an ever increasing number of in-patients.
In 1865, MRI purchased land in Cheadle for a Convalescent Hospital. Barnes Convalescent Hospital was opened in 1875, named after Robert Barnes, a cotton spinner who had donated £10,000 for the hospital (see Barnes Convalescent Hospital subsection). A site for a fever hospital was found at Monsall, also financed by Robert Barnes, this hospital was named the Barnes House of Recovery (see Monsall Hospital). These changes gave MRI more space, but the Infirmary was still insanitary, as was illustrated by a major outbreak of hospital disease in 1874. The 1870s saw the beginning of an era of specialisation. Both the Ophthalmic Department and Maternity Department were opened in 1872. The growth of specialist expertise within the MRI was consolidated with appointments of surgeons and physicians from the specialist hospitals. There were developments in the way the Infirmary was run. In 1875, MRI arranged for the District Provident Society to vet their patients. The old fashioned manner of electing medical staff was causing arguments, due to an over-emphasis on social status the most appropriate staff were often not elected. Despite strong public opposition from the trustees, the procedure was changed and appointments would be made by a Committee representing the trustees, advised by existing medical staff. A damning report on MRI by the Local Government Board led to alterations to the Infirmary. These were completed by 1880 and resulted in much improved conditions.
However, the arguments for an out of town site continued. The Whitworth Legacy enabled Owens College to purchase a large site on Oxford Road. When the Medical School merged with Owens College, there was a suggestion that MRI should do the same, bringing about greater integration between the hospitals and the College. At a special meeting of trustees on 4 December 1876, a move to Oxford Road was proposed and rejected. This rejection was largely due to fears of too close control by the medical school. This controversy dogged MRI for the last twenty years of the century. However, plans for an extension at Piccadilly met equally strong opposition; after a poll of 12,000 trustees, the proposal was heavily defeated and the Board of Management resigned. The deciding factor was probably the value of the Piccadilly site, which was sold to Manchester Corporation for £400,000. It decided to build a new hospital at Oxford Road in the pavilion style with 500 beds. The first patients moved to the new MRI in Oxford Road in 1908. A casualty station remained in the centre in the old out-patient department. This casualty station became known as the Central Branch and remained open until the Second World War forced its closure in 1943. MRI now formed part of a group of voluntary hospitals to the South of the University, a development which marked a rise in specialisation. During the First World War, 520 beds at MRI were allocated to the War Office. Between 1914 and 1919, over 10,000 soldiers were treated.
After the War, a number of developments took place at MRI. At the request of the Government, MRI set up a centre for the treatment of people suffering from venereal diseases. The Hospital collaborated closely with the Holt Radium Institute and Christie Hospital. A new Nurses Home was built in 1927. In 1932, it was decided to build a home for private patients. This required an act of parliament and in 1937 MRI opened a Private Patient's Hospital. MRI also built a new orthopaedic and physiotherapy block. During the Second World War the Infirmary continued to treate patients, despite bombing raids in which it suffered two direct hits and many blasts which caused damage to the hospital. MRI also provided many beds for the Emergency Medical Service. In the early 1940s, under a Joint Hospital Advisory Board scheme to provide local fracture clinics, a new orthopaedic block which had opened in 1939 was converted into a fracture unit for the Central Manchester Area. Sir Harry Platt was closely involved in this development of orthopaedics as a specialism. At the same time, Geoffrey Jefferson was involved in the emerging specialisation of neurology. A Neurological Department was built in 1951, under the directorship of Geoffrey Jefferson. The post-war period saw various progressive developments, including a department of clinical photography and a research centre for the study of chronic rheumatism. When the NHS was formed in 1948 MRI became part of the NHS. Along with St Mary's, the Dental and Foot Hospitals and the Royal Eye Hospital, MRI formed the Manchester Teaching Hospitals Group. There was major rebuilding in the 1980s and in 1991 MRI became part of a large acute NHS Trust, Central Manchester Healthcare Trust.