Background: African Americans are disproportionately affected by hypertension and have lower medication adherence when compared to other racial groups. Antecedent factors such as beliefs surrounding hypertension, the presence or absence of social support, and depressive symptoms have not been extensively studied collectively in relation to hypertension medication adherence in African Americans. Objective: To determine the associations among demographic and clinical factors, depressive symptoms, hypertension beliefs, and social support with blood pressure medication adherence in middle-aged African American adults with a diagnosis of hypertension. Methods: A cross-sectional study of (N = 120) African Americans (mean age, 49 years; 22.5% men) with a current diagnosis of metabolic syndrome, including hypertension, who reported having and taking a prescribed blood pressure–lowering medication were included. Descriptive statistics, bivariate correlation analysis, and logistic regression using odds ratio were used to examine the effects of high blood pressure beliefs, social support, and depression on medication adherence. Results: A small but significant relationship was found between medication adherence and number of comorbidities (r = 0.19, P = .04). In a multivariate regression model, after controlling for gender, comorbidities remained associated with medication adherence (β = 0. 77, P = .04). Depressive symptoms, high blood pressure beliefs, and social support did not have a significant relationship with medication adherence. Conclusions: Multiple comorbidities may have a positive impact upon medication adherence. Further study is needed in a larger sample of African Americans who have a diagnosis of hypertension in addition to other comorbidities requiring medication management.