Tintoretto’s narratives of the life and miracles of St Roch for the cappella maggiore of the Venetian church of San Rocco have been overshadowed by the master’s overwhelming achievement in the adjacent Scuola di San Rocco. Executed over several decades, the four laterali are usually analysed in isolation from each other and from their original placement and purpose. This article reintegrates these pictures as a coherent, planned sequence and suggests new readings in the light of confraternal, citywide and pan-European devotion to St Roch as a plague saint. Comparison with little-known earlier cycles of Roch, not previously brought to bear on Tintoretto’s paintings, sheds new light on artistic and patronal choices at San Rocco. In a carefully orchestrated interplay between visual imagery and embodied presence, Tintoretto’s paintings articulated the commissioning confraternity’s vision of their heavenly patron and shaped devotees’ approach to the saint, whose relics in the high altar were a magnet for those seeking protection against the scourge of bubonic plague.