Depression is a robust predictor of nonadherence to antiretroviral (ARV) therapy, which is essential to prevention of mother-to-child transmission (PMTCT). Women in resource-limited settings face additional barriers to PMTCT adherence. Although structural barriers may be minimized by social support, depression and stigma may impede access to this support.To better understand modifiable factors that contribute to PMTCT adherence and inform intervention development.We tested an ARV adherence model using data from 200 pregnant women enrolled in PMTCT (median age 28), who completed a third-trimester interview. Adherence scores were created using principal components analysis based on four questions assessing 30-day adherence. We used path analysis to assess (i) depression and stigma as predictors of social support and then (ii) the combined associations of depression, stigma, social support, and structural barriers with adherence.Elevated depressive symptoms were directly associated with significantly lower adherence (est = -8.60, 95% confidence interval [-15.02, -2.18], p < .01). Individuals with increased stigma and depression were significantly less likely to utilize social support (p < .01, for both), and higher social support was associated with increased adherence (est = 7.42, 95% confidence interval [2.29, 12.58], p < .01). Structural barriers, defined by income (p = .55) and time spent traveling to clinic (p = .31), did not predict adherence.Depression and social support may play an important role in adherence to PMTCT care. Pregnant women living with HIV with elevated depressive symptoms and high levels of stigma may suffer from low social support. In PMTCT programs, maximizing adherence may require effective identification and treatment of depression and stigma, as well as enhancing social support.