The church of Santo Spirito in Florence is universally accepted as one of the architectural works of Filippo Brunelleschi (1377-1446). It is nevertheless surprising that contrary to such buildings as San Lorenzo or the Old Sacristy, the church has received relatively little scholarly attention. Most scholarship continues to rely upon the testimony of Brunelleschi’s earliest biographer, Antonio di Tuccio Manetti, to establish an administrative and artistic initiation date for the project in the middle of Brunelleschi’s career, around 1428. Through an exhaustive analysis of the biographer’s account, and subsequent comparison to the extant documentary evidence from the period, I have been able to establish that construction actually began at a considerably later date, around 1440. It is specifically during the two and half decades after Brunelleschi’s death in 1446 that very little is known about the proceedings of the project. A largely unpublished archival source which records the machinations of the Opera (works committee) of Santo Spirito from 1446-1461, sheds considerable light on the progress of construction during this period, as well as on the role of the Opera in the realization of the church. In addition to collecting outstanding debts, the Opera also began to sell the rights of patronage over many of the church’s crossing chapels. The patrons of these chapels were members of the city’s republican elite. Much of the quarter’s social hierarchy is manifest in the church by the quantity of chapels owned by single families, rather than by chapel location. This is because Brunelleschi’s “centralized basilica” plan made traditional altar proximity less exclusive. Moreover, chapel patrons were surprisingly almost all exclusively residents of only three of the quarter’s four gonfaloni. The controversies concerning the completion of the church between 1471 and 1487, including the construction of an enclosing wall around Brunelleschi’s intended extruding semi-circular chapels, the hypothesis of barrel vaulting over the church, and the debate over the number of façade doors, suggest a general uncertainty about the architect’s original plan. My research into this post-Brunelleschian history of Santo Spirito focuses on the role of the cantiere (work site) as heir to Brunelleschi’s architectural inheritance; this also provides a means by which to insert the church into the wider context of the building tradition of fifteenth-century Florence. Like most cantieri of the time, the one at Santo Spirito was quite fluid in structure, with a panoply of laborers and suppliers providing the building site with various services and materials. The significant amount of unpublished documentation presented in this thesis concerning the cantiere also provides a succinct case study of the finances of ecclesiastical construction, and a revealing comparative analysis of the building costs of labor and materials at Santo Spirito in relation to other fifteenth-century building projects in Florence such as the hospitals of San Paolo and the Innocenti, as well as the Strozzi Palace.