OBJECTIVE Smoking cessation leads to both beneficial and harmful changes in cardiovascular disease (CVD) risk factors. The basis of the harmful changes, however, is unknown. Our objective was to determine whether they are associated with the weight gain that accompanies smoking cessation. METHODS Study subjects were male cigarette smokers aged at least 30 years who visited the Health Promotion Center of Seoul National University Hospital between 1995 and 2007 repeatedly with a 1- to 3-year interval between first and second visit. Self-reporting questionnaires gathered clinical and socio-economic characteristics on the initial visit, and CVD risk factors (blood pressure, fasting blood glucose, and serum lipid profile) were measured on both the visits. RESULTS We compared the CVD risk factors between smoking quitters and smoking continuers. The quitters were more likely than the continuers to have harmful health changes such as increase in body weight (P<0.01), in systolic blood pressure, and in serum levels of total cholesterol, LDL-cholesterol, and non-HDL cholesterol (P<0.05). When stratified by body weight change, quitters who had gained more than the median (1.3 kg) were more likely than those who had not to have increase in blood pressure (P<0.01) and in serum levels of total cholesterol, triglycerides, non-HDL cholesterol, and fasting glucose (P<0.05). CONCLUSIONS Harmful changes in CVD risk factors associated with smoking cessation were mainly secondary to weight gain. To reduce the risk of cardiovascular disease in quitters, therefore, more attention should be focused on preventing weight gain.