OBJECTIVE: To assess the relationship among Type D personality, self-efficacy, and medication adherence in patients with coronary heart disease. METHODS: The study design was prospective and observational. Type D personality, self-efficacy for illness management behaviors, and medication adherence were measured 3 weeks after hospitalization for acute coronary syndrome in 165 patients (mean [standard deviation] age = 61.62 [10.61] years, 16% women). Self-reported medication adherence was measured 6 months later in 118 of these patients. Multiple linear regression and mediation analyses were used to address the study research questions. RESULTS: Using the original categorical classification, 30% of patients with acute coronary syndrome were classified as having Type D personality. Categorically defined patients with Type D personality had significantly poorer medication adherence at 6 months (r = -0.29, p < .01). Negative affectivity (NA; r = -0.25, p = .01) and social inhibition (r = -0.19, p = .04), the components of Type D personality, were associated with medication adherence 6 months after discharge in bivariate analyses. There was no evidence for the interaction of NA and social inhibition, that is, Type D personality, in the prediction of medication adherence 6 months after discharge in multivariate analysis. The observed association between NA and medication adherence 6 months after discharge could be partly explained by indirect effects through self-efficacy in mediation analysis (coefficient = -0.012; 95% bias-corrected and accelerated confidence interval = -0.036 to -0.001). CONCLUSIONS: The present data suggest the primacy of NA over the Type D personality construct in predicting medication adherence. Lower levels of self-efficacy may be a mediator between higher levels of NA and poor adherence to medication in patients with coronary heart disease.