BACKGROUND: Patient trust in physicians is a critical determinant of health seeking behaviors, medication adherence, and health outcomes. A crisis of interpersonal trust exists in China, extending throughout multiple social spheres, including the healthcare system. At the same time, with increased migration from Africa to China in the last two decades, Chinese physicians must establish mutual trust with an increasingly diverse patient population. We undertook a qualitative study to identify factors affecting African migrants' trust in Chinese physicians and to identify potential mechanisms for promoting trust. METHODS/PRINCIPAL FINDINGS: We conducted semi-structured, in-depth interviews with 40 African migrants in Guangzhou, China. A modified version of the social ecological model was used as a theoretical framework. At the patient-physician level, interpersonal treatment, technical competence, perceived commitment and motive, and language concordance were associated with enhanced trust. At the health system level, two primary factors influenced African migrants' trust in their physicians: the fee-for-service payment system and lack of continuity with any one physician. Patients' social networks and the broader socio-cultural context of interactions between African migrants and Chinese locals also influenced patients' trust of their physicians. CONCLUSIONS: These findings demonstrate the importance of factors beyond the immediate patient-physician interaction and suggest opportunities to promote trust through health system interventions.