This paper explores the expansion of American mission nursing in Iran in the early to mid-twentieth century. Between 1916 and 1936, American mission nurses operated the only nursing schools in the country. Although they instigated cultural changes by establishing American forms of nursing, they did so through the agency of local Iranian women who adapted nurse training to suit their own purposes. Drawing on the extensive records of the American Presbyterian Historical Society, as well as oral interviews, memoirs, newspapers and photographs, this paper demonstrates that mission nurses’ efforts to promote international nursing standards in Iran intersected with Reza Shah’s modernizing initiatives in a way that served Iranian nationalism and state-building. I argue that Iranian nurses took advantage of mission nursing as an avenue for financial, social, geographical and professional mobility. I reveal that the emergence of nursing professionalism in Iran was shaped by the intertwining of local, transnational and global connections and expertise. My paper will demonstrate that mission nursing was used by women in Iran in various ways. Assyrian Christian nurses often used their connections with American missionaries to permanently relocate to the United States. Thus, American-mission nursing in Iran became a stepping stone to emigration. Persian Iranian women often embraced professional nursing and became prominent leaders in Iran’s Ministry of Health. They used their mission connections to secure fellowships and grants to study in the United States, which was a means of securing leadership positions within Iranian healthcare. The considerable scholarship on the history of health care in Iran, and the Middle East more broadly, rarely mentions nurses. In recent years, historians have published a number of important works that critically explore the history of medical education, professionalization and practice in Iran, but nursing is rarely explored in these studies. My research makes a valuable contribution to the field. Colonial medicine was never unidirectional but rather a meaningful interaction with unintended consequences. My nursing-focused study will demonstrate that the Iranian government utilized American mission nurses in the development of state medicine, and that many of Iranian nurses who trained in mission-run nursing schools became leaders of the Iranian nursing profession.