The Henderson Fire Department responded to a fire at the former Gilmore Inn on Washington Street.
The fire came in around 3 am, Wednesday at the Simple Rewards Inn which now serves as week-to-week apartments.
Henderson Firefighters say the fire started on the 2nd floor of the building and they are still working to put out hot spots in the attic.
A city bus was brought in to keep the residents, who were evacuated from the building, warm.
Volunteers from the Red Cross of Owensboro then arrived and the residents were taken to the Ramada Inn, which is under the same ownership as Simple Rewards.
No one was injured during the initial response and evacuation.
According to the fire chief, the building is a total loss. The 150-year-old building was the first hospital in Henderson County.
Multiple departments assisted HFD during the call.
The hotel owner also runs the Economy Inn and Suites on Highway 41 says donations of coats, blankets, or food for the displaced residents can be dropped off there.