OBJECTIVE: To determine operative mortality in surgical programs from resource-limited settings. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 17 surgical programs in 13 developing countries by 1 humanitarian organization, Médecins Sans Frontières, was performed between January 1, 2001, and December 31, 2008. Participants included patients undergoing surgical procedures. MAIN OUTCOME MEASURE: Operative mortality. Determinants of mortality were modeled using logistic regression. RESULTS: Between 2001 and 2008, 19,643 procedures were performed on 18,653 patients. Among these, 8329 procedures (42%) were emergent; 7933 (40%) were for obstetric-related pathology procedures and 2767 (14%) were trauma related. Operative mortality was 0.2% (31 deaths) and was associated with programs in conflict settings (adjusted odds ratio [AOR] = 4.6; P = .001), procedures performed under emergency conditions (AOR = 20.1; P = .004), abdominal surgical procedures (AOR = 3.4; P = .003), hysterectomy (AOR = 12.3; P = .001), and American Society of Anesthesiologists classifications of 3 to 5 (AOR = 20.2; P < .001). CONCLUSIONS: Surgical care can be provided safely in resource-limited settings with appropriate minimum standards and protocols. Studies on the burden of surgical disease in these populations are needed to improve service planning and delivery. Quality improvement programs are needed for the various stakeholders involved in surgical delivery in these settings.