[1] The earliest records of the hospital can be traced to the presence of Bang Rak Hospital at the junction of Silom and Charoen Krung Roads, run by American doctor Thomas Heyward Hays.

Lerdsin was also the hospital where injured soldiers and civilians were treated following the Paknam incident.

During the Second World War, Lerdsin Hospital was damaged following the Bombing of Bangkok and general treatment was temporarily halted, while only the STI unit remained open.

Following the war after years of successful operation of the STI unit, it became upgraded to the Division of Sexually-transmitted Infection Control of the Department of Medical Services (DMS) and hospital operations were transferred to the DMS and renamed Lerdsin Hospital.

In 2013, Lerdsin Hospital cooperated with the College of Medicine, Rangsit University to provide medical education.