For patients to manage their medication regimens at home, adequate preparation is required prior to hospital discharge. Self-administered medication programs are a strategy for improving medication knowledge and regimen adherence. The purpose of this study was to evaluate the effectiveness of a self-administered cardiac medication program on patients knowledge of and adherence to their medication regimen. Patient and nurse satisfaction with the self-administered medication program were assessed. A comparison group, repeated measures design was used in which patients received nurse-administered medications (n = 172) or self-administered medications (n = 178). Data were collected at admission, discharge, and 2, 6, and 16 weeks post-discharge. Outcome variables were medication knowledge, medication adherence, and program satisfaction. Patients in the self-administered medication group had significantly higher medication knowledge scores over time compared to those in the nurse-administered medication group. There was no statistically significant difference between groups on medication adherence. The self-administered medication group reported significantly higher levels of satisfaction and had significantly fewer medication errors and medication-related problems compared to the nurse-administered medication group.