BACKGROUND: Racial/ethnic health care disparities are well described in people living with HIV/AIDS, although the processes underlying observed disparities are not well elucidated. METHODS: A retrospective analysis nested in the University of Alabama at Birmingham 1917 Clinic Cohort observational HIV study evaluated patients between August 2004 and January 2007. Factors associated with appointment nonadherence, a proportion of missed outpatient visits, were evaluated. Next, the role of appointment nonadherence in explaining the relationship between African American race and virologic failure (plasma HIV RNA >50 copies/mL) was examined using a staged multivariable modeling approach. RESULTS: Among 1221 participants, a broad distribution of appointment nonadherence was observed, with 40% of patients missing at least 1 in every 4 scheduled visits. The adjusted odds of appointment nonadherence were 1.85 times higher in African American patients compared with whites [95% confidence interval (CI) = 1.61 to 2.14]. Appointment nonadherence was associated with virologic failure (odds ratio = 1.78, 95% CI = 1.48 to 2.13) and partially mediated the relationship between African American race and virologic failure. African Americans had 1.56 times the adjusted odds of virologic failure (95% CI = 1.19 to 2.05), which declined to 1.30 (95% CI = 0.98 to 1.72) when controlling for appointment nonadherence, a hypothesized mediator. CONCLUSIONS: Appointment nonadherence was more common in African American patients, associated with virologic failure, and seemed to explain part of observed racial disparities in virologic failure.