American Protestant missionaries had tremendous success in the entire Ottoman domains in the 19th century (especially in the last quarter of it) and left a remarkable collection of primary sources. Despite many studies done by a multitude of scholars in different fields, there is a need for in-depth studies of the women missionaries in the Near East missions. This paper will look closely into the work of a select group of women missionaries who worked in the medical field in the Ottoman Empire towards the end of the 19th and early 20th centuries. Women missionaries developed an empathetic view of their host countries compared to their male counterparts and worked to empower local women: educating them in women’s colleges in the cities, and in rural places training them in vocational schools. They also deeply influenced the development of modern health care in host countries. Even though the American missionaries were particularly successful among the Orthodox and Armenian Christian communities in the empire, many born-Muslim women were matriculated in the various schools in the empire and received care in the mission hospitals. The studies on the women missionaries of the Near East Mission are still few and far between. A recent and noteworthy exception (and contribution to this field) came from Barbara Reeves-Ellington in her book Domestic Frontiers: Gender, Reform, and American Interventions in the Ottoman Balkans and the Near East (2013). The recent scholarship on ABCFM displays that American missionaries were far from a monolith particularly as far as the gender aspect is concerned. Women missionaries were working in hospitals providing care in difficult conditions. Unlike their male counterparts, they were entering easily into the female space in a society in which male and female segregation was the norm not only among the Muslim subjects of the empire but also among the Armenian and Greek subjects. This way, they were also generating unique insights into the Ottoman society and culture, which would otherwise may not possible by the male missionaries to generate. Based on ABCFM archives housed in Harvard University’s Houghton Library, Andover-Harvard Theological library, and the Mary I. Ward Papers and Grace H. Knapp Papers, housed in Mount Holyoke College Archives, this paper will investigate the role women missionaries played particularly in the medical field in the late Ottoman Empire.