The hospice was built to provide hospitality to pilgrims and wayfarers traveling along the Via Pisana. It was built between 1416 and 1421 by the guild of silk-makers, Consoli dell’Arte della Seta, and according to a will left by Francesco di Leccio da San Miniato. Hospices were run by religious orders or guilds, such as the Arte della Seta in this case, and primarily catered to the poor.
Its architectural features, like those of the Spedale di San Matteo in Piazza San Marco in Florence, were a model for the construction of Florence’s Spedale degli Innocenti, designed by Brunelleschi.
The hospice’s seven-arch portico offered shelter to wayfarers and featured large wooden doors, which opened onto the halls on the ground floor.
Unlike those in town, the hospices in the rural areas experienced a decline which impacted Sant’Antonio as early as 1642.
At the end of the 18th century the portico began to house merchants selling foodstuffs. In 1785 it was purchased by a private citizen, who restyled and transformed the entire building was. It later served diverse purposes and even came to house the Teatro della Fenice, inside the hall of the left wing, during the early 19th century.