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Renaissance hospitals were complex sites of both exchange and sequestration. The hospital of Santa Maria della Scala in Siena was not only a home for the sick and orphaned, but also an economic hub, and a hostel for pilgrims and travelers from all social stations. This paper addresses the permeability of hospital walls, which created differentiated spaces while also linking the institution to its larger urban environment, by examining the fifteenth-century frescoes in the pilgrim’s hall of Santa Maria della Scala. These frescoes explicitly reference the walls on which they are painted, showing both the construction of the hospital as well as its charitable activities framed by representations of the hospital interior, populated by diverse groups of travelers and the needy. The scenes, I will argue, situate the urban hospital as a place of both worldly exchange and protection and care, contributing to Siena’s image as an ideal virtuous city.