The papacy was actively involved in the Eastern Mediterranean throughout the fourteenth century, and evidence of much of its activity can be found in the registers preserved in the Vatican Archives. By using a source base of nearly 1,300 letters drawn from the registers directly relating to activity in the Eastern Mediterranean and supporting non-papal evidence, this thesis explores the aims, intentions, and outcomes of papal policy toward the East. The Eastern Mediterranean during the Avignon period was a site of exchange, trade, and conflict, and the papacy was actively involved in controlling behaviour and propagating its own agenda. An analysis of these policies and interventions allows for an evaluation of the papacy’s ability to establish and maintain authority and exercise power. This thesis contextualises the reasons why the papacy was able to act, or was unable to act, alongside the intentions of the papacy, for a greater understanding of the popes’ influence and activity in the region. The papacy clearly maintained a consistent interest in the East throughout the Avignon period and enacted a series of policies designed to control the behaviour of Catholics living and working in the East, increase its influence over other Christian Churches, and engage with non-Christian political powers. Most individuals, institutions, and polities accepted the authority of the papacy, but the power of the papacy was limited. It was largely unable to enforce its will even though most actors in the Eastern Mediterranean accepted its right to impose its agenda. Despite this lack of power, respect for the papacy’s authority led to some significant achievements, and the evidence base demonstrates a complicated series of policies aimed at securing Catholic interests.