Beginning in the summer of 1629, a wave of the plague assaulted Venice, and over the next two years killed nearly a third of the population. In the city 46,000 people died whilst in the lagoons the number was far higher, some 94,000. Repeated displays of the sacrament, as well as prayers and processions to churches dedicated to San Rocco and San Lorenzo Giustiniani had failed to stem the epidemic. Echoing the architectural response to a prior assault of the plague (1575–76), when Palladio was asked to design the Redentore church, the Venetian Senate on October 22, 1630, decreed that a new church would be built. It was not to be dedicated to a mere "plague" or patron saint, but to the Virgin Mary, who for many reasons was thought to be a protector of the Republic.
It was also decided that the Senate would visit the church each year. On November 21 the Feast of the Presentation of the Virgin, in a celebration known as the Festa della Madonna della Salute, the city's officials parade from San Marco to the Salute for a service in gratitude for deliverance from the plague. This involved crossing the Grand Canal on a specially constructed pontoon bridge and is still a major event in Venice.