We conducted a prospective, open-label trial to evaluate the effectiveness of a pharmacist-based, comprehensive, smoking-cessation program with 31 self-referred subjects. A secondary goal was to measure changes in health-related quality of life (HRQOL) during the cessation attempt. The program consisted of weekly, 1-hour group sessions over 12 weeks. It incorporated nicotine replacement therapy (patch, gum) with extensive behavior modification counseling. Trained pharmacists served as program facilitators. Smoking cessation was chemically verified at 3 and 6 months by exhaled carbon monoxide. The patients' HRQOL was measured using the smoking-cessation quality of life questionnaire at baseline, 2 weeks, and 1, 2, 3, and 6 months. Chemically verified abstinence rates at 3 and 6 months were 42% (13 patients) and 26% (8 patients), respectively. Among patients who quit, vitality, mental health, and self-control significantly improved during the 3-month program. Six-month cessation rates were modest, although HRQOL improved within 3 months of abstinence.