The hospital was founded in 1221 to provide assistance to pilgrims and the ill; in 1403 it was enlarged, for the precise purpose of providing accommodation for sick persons dismissed from other Florentine hospitals during their period of convalescence. Here the patients stayed an average time of eight days, nourished on an abundant diet, in a comfortable environment, assisted by nurses and Oblates, before being definitively dismissed and returning to their homes.

In the second half of the 15th century, a loggia was built as an extension to the Hospital. It is commonly known as the Loggiato delle Leopoldine due to the fact that it housed, in the 18th century, the schools founded by Grand Duke Peter Leopold. It is composed of ten arcades, in which the tondos with images of the saints by Andrea della Robbia can still be admired today.

In 1780, following an inspection carried out by the grand-ducal physician Antonio Cocchi, who declared this institute to be inadequate to its purpose, Peter Leopold decreed its suppression and the transfer of its belongings to the Hospital of Santa Maria Nuova.

Since late 2006, the building has become the new seat of the Alinari Brothers Museum of the History of Photography.