The first written mention of HST was on April 11, 1703, in a letter by Juan de Argüeyes, the Bishop of Panama City to King Philip V of Spain where he told him about a hospice he founded and that had been working since the day of Saint Thomas of Villanueva, September 22, 1702 to treat poor women who had nowhere to go and he begged him to bear to this hospice the title of hospital.

On September 1, 1924, a new complex of buildings was built at the present location, on Balboa Avenue under the administration of President Belisario Porras who wanted to give the country a new, modern hospital.

Opposition politicians criticized the project, calling it a white elephant because they said it was too big for a small country.

As a result, the HST takes care of people 15 years old and up, and refers cancer patients to the National Oncologic Institute.

Some buildings were evacuated but maintained as they are considered historical landmarks and plans are in progress to renovate them as a museum or administrative offices for the hospital.