Sydenham Hospital, 1925.

Sydenham opened as a private hospital in a Harlem brownstone in 1892. The hospital served mostly African-American patients who lived in the neighborhood. To meet the needs of its growing community, Sydenham moved to West 125th Street and Lenox Avenue in 1924. Though Harlem was a largely African-American neighborhood, the staff of the hospital was reported to be all-white in 1944; likely due to the fact that discrimination within the medical community left little to no opportunities for African American healthcare professionals. To amend this, the hospital employed a desegregation policy, which was radical at the time. Sydenham hired twenty African Americans to its staff and brought six African Americans onto its Board, making it the first full-service hospital to hire black physicians. By 1947, the New York Times wrote that it was "praised...for its inter-racial activities...an example for the entire world," by Eleanor Roosevelt, who spoke at a fundraiser on behalf of the hospital. After the fundraiser, the director Dr. Sigmund L. Friedman made the statement that Sydenham was "the best place to prove that race, creed, and color have no importance in the hospital."

The fundraiser that Mrs. Roosevelt spoke at was just one of many attempts to keep the hospital fiscally afloat. Throughout its existence, Sydenham was ridden with money problems. Finally bending to financial strain in 1949, the hospital was transferred from private ownership to New York City's municipal hospital system, though it allowed private patients to continue seeing doctors at Sydenham to "preserve the interracial practice of the hospital."

In 1979, Sydenham Hospital became the center of a massive walk-out staged by the Committee for Interns and Residents. When Ed Koch took office as the Mayor in 1977, he reduced city spending on all municipal hospitals. Two hospitals in Harlem, Sydenham and Metropolitan, were slated for closure. Harlem was a "medically underserved area," and the two public hospitals were vital for the community's wellbeing. Additionally, Sydenham's sickle cell anemia clinic, led by Florence Gaynor, was of importance to the medical community at large. Unfortunately, countless public rallies and demonstrations were ignored by the city and in 1980, the city officially closed Sydenham. The hospital was subsequently occupied by "The People's Administration," for 10-days of protest, who brought national attention to the importance of the hospital. Sydenham's demise provided a cautionary lesson. In 1998, reflecting on the changing terrain of public healthcare in New York City, Sharon Lerner wrote in the Village Voice: "The Sydenham blunder paved the way for today’s more clandestine approach to hospital downsizing, in which the city reduces its contribution to the Health and Hospitals Corporation and the agency is thereby ”forced” to make cuts to the public hospitals."