The hospital expanded continuously throughout the late 19th century, adding an outpatient dispensary in 1888, a school of nursing in 1892, and additional beds and services in 1892, 1893, 1904 and 1912.

Presbyterian Hospital was founded by James Lenox in 1868, and began operations in 1872, in buildings designed by Richard Morris Hunt.

The hospital moved to a new James Gamble Rogers-designed facility, which included the Harkness Pavilion for private patients and the Squier Urology Clinic,[4] in 1928.

"[5] The Federal Writer's Project's Guide to New York City, published in 1940, extolled the virtues of the 1928 building, and the other original building of the Medical Center, as "among the pioneering structures of the late 1920s when traditional styles were being abandoned in favor of a utilitarian approach," with large flat windows to provide the maximum amount of natural light.

The AIA Guide to New York City, on the other hand, says the flat windows are "bulky and banal" and calls the streetscape "a bore".