Stressful and traumatic life events (STLEs) are common among HIV-infected individuals and may affect health behaviors such as adherence to antiretroviral (ARV) therapy, with important implications for treatment outcomes. We examined the association between STLEs and ARV adherence among 289 US-based participants enrolled between 7/1/2010 and 9/1/2013 in a study of depression treatment for HIV-infected patients. Participants received monthly telephone calls to assess STLEs and pill count-based ARV adherence. Inverse probability of observation weighting was combined with multiple imputation to address missing data. Participants were mostly male (71%) and black (63%), with a median age of 45 years. Median monthly adherence was 96% (interquartile range (IQR): 85-100%). Participants experienced a mean of 2.48 STLEs (range: 0-14) in the previous month. The presence of ≥2 STLEs was associated with a mean change in adherence of -3.67% (95% confidence interval (CI): -7.12%, -0.21%) and decreased likelihood of achieving ≥95% adherence (risk ratio (95% CI) = 0.82 (0.71, 0.95)). For each additional STLE, the mean adherence change was -0.90% (95% CI: -1.79%, 0.00%). STLEs were associated with poorer ARV adherence, including decreased likelihood of adhering to ≥95% of ARV doses. This level of adherence has a critical role in regimen effectiveness and prevention of resistance.