Weight gain is frequent after smoking cessation, and may limit patient's will to quit and long-term success. Nicotine and bupropion are effective drugs for smoking withdrawal. However, their influence on weight gain, insulin resistance and other cardiovascular risk factors, as well as possible differences in obese and lean subjects, have not been fully evaluated. We randomised 25 lean and 25 obese smokers to receive either bupropion or nicotine patches. Clinical evaluation and lipid profile were performed at baseline and after treatment. Insulin resistance was also assessed at the end. Weight, BMI, waist-to-hip ratio, and diastolic blood pressure increased (p < 0.005), whereas lipid profile improved (p < 0.001) after smoking cessation independently of obesity at baseline or drug used. Obese patients had higher insulin resistance at the end (p < 0.05) regardless of drug used. Weight gain was inversely related to age (beta= - 0.125, R = 0.38, p = 0.046), and insulin resistance was related to obesity at baseline (beta = 0.85, R = 0.46, p = 0.02). In conclusion, weight gain after smoking cessation is not dependent on obesity or drug taken. A beneficial lipid profile is achieved after quitting smoking with either bupropion or nicotine patch in both obese and lean subjects.