We aimed to detect the synergistic effect between alcohol drinking, smoking and obesity on incident cardiovascular disease (CVD) in a Chinese population- based cohort.We performed this study based on a prospective cohort based on a Chinese population in Jiangsu, China. Logistic regression was employed to detect the interaction of smoking, drinking with obesity on susceptibility to CVD, and calculate the odds ratio (OR) of CVD and corresponding 95% confidence interval (CI).A total of 3598 subjects (1451 males and 2147 females) were enrolled, including 82 CVD patients (36 males and 46 females) who new developed CVD at the follow-up. We found a significant abdominal obesity-current smoking interaction on CVD risk. Compared to never-smokers with normal waist circumference, OR (95% CI) of CVD were 2.44 (1.56-3.81), 1.58 (0.93-2.69), and 5.37 (3.08-9.34) for smokers with normal waist circumference, abdominal obese nonsmokers and abdominal obese smokers, respectively. Synergy index for this interaction was 2.35 (1.05-4.50). We also found a significant abdominal obesity-alcohol drinking interaction on CVD. Compared to never-drinkers with normal waist circumference, OR (95% CI) of CVD were 1.57 (1.01-2.45), 1.84 (1.08-3.12), and 4.44 (2.55-7.72) for drinkers with normal waist circumference, abdominal obese non- drinkers and abdominal obese drinkers, respectively. Synergy index for this interaction was 2.44 (1.04-5.72).We found significant interactions between alcohol drinking and abdominal obesity, smoking and abdominal obesity on CVD risk, suggested that the effect of alcohol drinking or smoking on CVD susceptibility seems to be modified by abdominal obesity.