Medication non-adherence is common and a primary reason for poor medical outcomes among individuals with heart failure (HF). This study's aims were to determine whether depression, hostility, and the personality-based Millon Behavioral Medicine Diagnostic (MBMD) Medication Abuse scale were associated with medication adherence (e.g., beta-blockers, ACE inhibitors, diuretics, statins) beyond contributions of demographic, medical, and psychosocial variables in an ethnically-diverse sample of 105 men and women diagnosed with HF. In hierarchical regression, greater MBMD Medication Abuse scale scores were associated with poorer adherence above and beyond both depression (β = .236, t = 2.113, p = .037) and hostility (β = .244, t = 2.506, p = .014). The Medication Abuse scale also completely mediated the relationship between adherence and depression. These findings suggest that personality measures such as the MBMD and hostility scales might be utilized in future studies investigating predictors of adherence and also used clinically to predict medication adherence among HF patients.