BACKGROUND Cigarette smoking is a well-known major risk factor in coronary heart disease. Smoking cessation results in a positive change in atherogenic factors. High-density lipoprotein cholesterol has been observed as increasing with smoking cessation. Since the use of nicotine transdermal replacement has become so widespread, this study examined the effect, if any, of the transdermal nicotine system on selected cardiovascular parameters in patients who were abstinent from cigarette smoking, and possible dose effect. METHODS Eight cardiovascular outcome measures were evaluated at baseline and Week 6 in both abstinent and non-abstinent patients randomized to four treatment groups; transdermal nicotine system 7 mg, 14 mg, and 21 mg per day, and placebos. RESULTS In abstinent patients, systolic blood pressure and heart rate decreased from baseline (while still smoking, before the start of the study) to the end of transdermal treatment, while weight increased. Similarly, HDL increased while LDL decreased and triglycerides increased. In nonabstinent patients, weight also increased from baseline to Week 6 while heart rate decreased. No other variables showed significant change. In abstinent patients, effect of nicotine dosage was observed with greater weight gain in placebo than 21 mg TTS patients and greater decrease in heart rate in placebo than 21 mg TTS patients. CONCLUSIONS In summary, the abstinent patients showed a positive effect of smoking cessation on cardiovascular risk factors even while using the transdermal nicotine system. These findings are favorable since the transdermal nicotine system has become a useful method of nicotine replacement in smoking cessation programs.