This study examined the role of a Medication Event Monitoring System (MEMS) to assess pill-taking behavior and enhance compliance within a randomized trial of bupropion-SR for smoking cessation. Female participants (N = 97) received MEMS bottles containing bupropion-SR 150 mg or placebo, to be taken twice daily. A randomly selected "feedback" group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance. A "no-feedback" group was not informed about the MEMS bottles, and did not receive further instruction or feedback beyond the standard dosing instructions. Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval. Results indicated significantly higher compliance over time for the feedback group. Participation in the feedback group predicted higher compliance beyond demographic, smoking, and health belief variables, suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen.