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Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust-HIV conspiracy beliefs (eg, HIV is genocide against African Americans)-was associated with antiretroviral treatment nonadherence among African American men with HIV.On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, sociodemographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one month postbaseline among 177 men in the baseline sample.Confirmatory factor analysis revealed 2 distinct conspiracy belief subscales: genocidal beliefs (eg, HIV is manmade) and treatment-related beliefs (eg, people who take antiretroviral treatments are human guinea pigs for the government). Both subscales were related to nonadherence in bivariate tests. In a multivariate logistic regression, only treatment-related conspiracies were associated with a lower likelihood of optimal adherence at one-month follow-up (odds ratio = 0.60, 95% confidence interval = 0.37 to 0.96, P < 0.05).HIV conspiracy beliefs, especially those related to treatment mistrust, can contribute to health disparities by discouraging appropriate treatment behavior. Adherence-promoting interventions targeting African Americans should openly address such beliefs.