In 1257 Pope Alexander IV revoked the interdiction cast on Pisa and the Pisans by Gregory IX, on condition they built a new hospital. This was the beginnings of the Fabbrica dell’Ospedale Nuovo called “della Misericordia” or “Alexander I’s” later “di Santo Spirito” and finally, “di S. Chiara”.

Giovanni di Simone was the architect of the project. He designed a quadrangular construction, each side 150 metres long with a tower at each corner. Traces of the oldest parts can still be seen in the two buildings on via Roma and in the remains of towers on the corner between via Roma and the Cathedral place. The northern front was only completed in 1337, when the peregrinario degli infermi (today Museum of Preparatory Drawings) was finished. Many activities went on within the walls: documents tell of a granary, a bakery, a cellar, tailors’ and metalworkers workshops and at least one garden where medicinal herbs were grown for the preparations sold in the pharmacy.

The present perimeter incorporates a stretch of the 12th century city walls and one of the gates, porta Buoza is still visible. In 1262, thanks to a donation, the chapel of S. Spirito was joined by the S. Chiara chapel with an adjacent graveyard. (1277). From 1545 to 1771 the Spedalinghi managed the hospital; 19 of their coats of arms decorate the arcade of the Spedalinghi courtyard, entered from via Roma.

Over time many new buildings of considerable architectural interest have been erected to accommodate new hospital facilities and University clinics, in particular, during the 19th and 20th centuries.