Statement of Significance (as of designation - September 25, 1997):
This hospital represents early federal efforts in health care and social welfare. In 1798, Congress established the Marine Hospital Fund, which, by 1912, evolved into the U.S. Public Health Service. The Louisville hospital was built between 1845 and 1852 and is the best of the few surviving examples of some 30 hospitals built before the Civil War, including 7 authorized by Congress in 1837 for construction on the "Western Waters." Built from standardized plans developed by architect Robert Mills, it exemplifies the latest ideas in hospital design of its time but is now used only for storage.

In 2003, the United States Marine Hospital, received a Save America's Treasures matching grant in the amount of $375,000 to replace the roof and perform other exterior work to weatherproof the building.