In 1892 it moved to purpose-built premises on Austin Street, Bethnal Green, to serve the population of the nearby Old Nichol rookery and, later, the Boundary Estate.

After extensive campaigning by Helen Taylor Thompson and others, in 1985 Mildmay was reopened, first as a nursing home and then as an AIDS hospice; in 1988, it resumed operations in new premises at Tabernacle Gardens, off Hackney Road, and has remained primarily dedicated to HIV/AIDS care since.

Despite its strong evangelical Christian orientation, patients were admitted regardless of religion, and the hospital often treated members of the East End's Jewish community.

[8] In anticipation of slum clearances by the London County Council, construction was begun in 1890 of a new, larger hospital on Austin Street off Hackney Road; it opened in 1892 with 50 beds and additional staff.

However, loss of staff positions and pressure to reduce NHS spending made the proposal untenable, and in September 1982 it was rejected in favour of the hospital's closure.

[10] On the basis of a feasibility study conducted the year before and presented to Norman Fowler, then Secretary of State for Health and Social Services, it was finally proposed that the facility be reopened as a voluntary charitable hospital, fully independent of the NHS.

Until late 1986, the patient population comprised chronically ill and disabled young adults from the community, as well as convalescents who were well enough to be discharged from acute hospital beds but needed further care.

[14] Despite initial resistance both from church leaders on the Mildmay board and from organisations representing the gay community, a rapport was quickly established, and in January 1987 work was started to convert one of the nursing home's wards into a dedicated AIDS hospice, which would become the first of its kind in Europe.

[14] Several members of the hospital's medical staff (including Veronica Moss, its superintendent since October 1986) made visits to San Francisco to learn more about HIV/AIDS and current care practices.

[15][2] During the COVID-19 pandemic in the United Kingdom, Mildmay became the main referral hospital for homeless Londoners with COVID-19 requiring non-intensive inpatient care, via the so-called Step-Down COVID-Care Pathway.

[1] Four inpatient beds were designated for this purpose, and referrals were accepted from outreach teams and homeless hostels, including of patients not registered with a GP.

[18] In 2020, Mildmay was again threatened with closure as clinical commissioning groups (CCGs) objected to its high rates of admission of patients from outside East London and elsewhere in the UK.