Heart failure (HF) is a global public health problem, and outcomes remain poor, especially among ethnic minority populations. Medication adherence can improve heart failure outcomes but is notoriously low. The purpose of this secondary analysis of data from a prospective cohort comparison study of adults with heart failure was to explore differences in predictors of medication nonadherence by racial group (Black vs. White) in 212 adults with heart failure. Adaptive modeling analytic methods were used to model HF patient medication nonadherence separately for Black (31.7%) and White (68.3%) participants in order to investigate differences between these two racial groups. Of the 63 Black participants, 33.3% had low medication adherence, compared to 27.5% of the 149 White participants. Among Blacks, 16 risk factors were related to adherence in bivariate analyses; four of these (more comorbidities, lower serum sodium, higher systolic blood pressure, and use of fewer activities compensating for forgetfulness) jointly predicted nonadherence. In the multiple risk factor model, the number of risk factors in Black patients ranged from 0 to 4, and 76.2% had at least one risk factor. The estimated odds ratio for medication nonadherence was increased 9.34 times with each additional risk factor. Among White participants, five risk factors were related to adherence in bivariate analyses; one of these (older age) explained the individual effects of the other four. Because Blacks with HF have different and more risk factors than Whites for low medication adherence, interventions are needed that address unique risk factors among Black patients with HF.