Medication nonadherence increases the risk of hospitalization and poor outcomes, particularly among patients with cardiovascular disease. The purpose of this study was to examine characteristics associated with medication nonadherence among adults hospitalized for cardiovascular disease. Patients in the Vanderbilt Inpatient Cohort Study who were admitted for acute coronary syndrome or heart failure completed validated assessments of self-reported medication adherence (the Adherence to Refills and Medications Scale), demographic characteristics, health literacy, numeracy, social support, depressive symptoms, and health competence. We modeled the independent predictors of nonadherence before hospitalization, standardizing estimated effects by each predictor's interquartile range. Among 1,967 patients studied, 70.7% indicated at least some degree of medication nonadherence leading up to their hospitalization. Adherence was significantly lower among patients with lower health literacy (0.18-point change in adherence score per interquartile range change in health literacy), lower numeracy (0.28), lower health competence (0.30), and more depressive symptoms (0.52) and those of younger age, of non-White race, of male gender, or with less social support. Medication nonadherence in the period before hospitalization is more prevalent among patients with lower health literacy, numeracy, or other intervenable psychosocial factors. Addressing these factors in a coordinated care model may reduce hospitalization rates.