This Institution, known as the Bush Hill or the Smallpox Hospital, was established by an act of legislature in the early part of the nineteenth century. It occupied, with its grounds, the entire square between 19th and 20th Streets, below what was then Coates Avenue.

Established in 1810, the general construction of the hospital consisted of a main building fronting fifty feet, three stories high, with two wings, each one hundred feet in length and two stories in height. It was under the control and management of the Board of Health of Philadelphia, and was a public hospital for the reception and treatment of all persons "who [were] afflicted with any pestilential or contagious disease."

The diseases treated in the Hospital were confined chiefly to smallpox and typhus (also called ship fever). During yellow fever and cholera epidemics, common in Philadelphia, a large share of the cases were received into and treated in this hospital; many of those who died were buried on the grounds there. The burial ground may have been used previously for interments of those who died in the temporary Bush Hill hospital during the infamous 1793 epidemic of yellow fever, but after 1810, the burial ground was used for patients who died in the hospital.

Previously, those who died at a temporary City Hospital established at the Wigwam Tavern during the yellow fever epidemic of 1797 were buried at a burial ground located at Race Street, between 22nd and 23rd Streets.

When the hospital was located and erected in 1810, it was in an isolated and healthy spot, more than two miles beyond the center of population, and to the northwest of what is known in the annals of Philadelphia, as Bush Hill, once the country-seat of James Hamilton, Esq., Colonial Governor of the Province of Pennsylvania, in 1760. But the rapid and steady march of development of the city rendered it no longer suitable, much less desirable for use as a pest hospital, and in 1858, the City Council passed an ordinance for its removal to a more eligible location, about two miles due north at 22nd and Lehigh.