BACKGROUND: Vertical HIV programs have achieved good results but may not be feasible or appropriate in many resource-limited settings. Medecins sans Frontieres has treated HIV in vertical programs since 2000 and over time integrated HIV treatment into general health care services using simplified protocols. We analyzed the survival probability among patients receiving antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical programs in 9 countries in sub-Saharan Africa. METHODS AND FINDINGS: Cox regression assessed mortality and program design association, adjusting for baseline age, body mass index, clinical WHO stage, tuberculosis, program age and setting. The analysis included 15,403 HIV-positive adults on ART in 7 vertical (14,124 patients) and 10 integrated (1279 patients) programs. Cox regression including 14,523 patients followed for up to 30 months ART showed similar outcomes for mortality (adjusted hazard ratio (aHR) 1.02; 95% confidence interval (CI): 0.83 to 1.24) and lower risk of loss to follow-up (aHR: 0.71; 95% CI: 0.61 to 0.83) in integrated compared with vertical programs. The greatest risk of death was from initiating ART at WHO stage 4 (aHR 1.99, 95% CI: 1.74 to 2.29), although greater program experience was protective (aHR: 0.77, 95% CI: 0.66 to 0.89). Risk of loss to follow-up was greater in experienced programs (aHR: 3.33; 95% CI: 2.92 to 3.79) and rural settings (aHR: 3.82; 95% CI: 3.49 to 4.20). CONCLUSIONS: ART delivery in integrated general health care programs results in good outcomes. Compared with vertical HIV programs, patients initiated ART in integrated programs at more advanced stages of clinical immunosuppression yet had similar risk of death and lower risk of loss to follow-up.