People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD. We included Third National Health and Nutrition Examination Survey participants who either reported no alcohol consumption or preferentially drinking wine with total alcohol consumption up to 10 g per day. Suspected NAFLD was based on unexplained serum alanine aminotransferase (ALT) elevation over the cut point of the reference laboratory (ALT > 43) and the cut point based on the 95th percentile of healthy subjects (ALT > 30 for men; ALT > 19 for women). Multivariate analysis was adjusted for age, gender, race, neighborhood, income, education, caffeine intake, and physical activity. A total of 7,211 nondrinkers and 945 modest wine drinkers comprised the study sample. Based on the reference laboratory cut point, suspected NAFLD was observed in 3.2% of nondrinkers and 0.4% of modest wine drinkers. The adjusted odds ratio was 0.15 (95% confidence interval, 0.05-0.49). Using the healthy subject cut point, suspected NAFLD was observed in 14.3% of nondrinkers and 8.6% of wine drinkers. The adjusted odds ratio was 0.51 (95% confidence interval, 0.33-0.79). Conclusion: Modest wine consumption is associated with reduced prevalence of suspected NAFLD. The current study supports the safety of one glass of wine per day for cardioprotection in patients at risk for both coronary heart disease and NAFLD. (HEPATOLOGY 2008;47:1947-1954.) T he beneficial effects of wine and wine-derived chemicals have received a great deal of recent attention. Moderate wine consumption has been associated with reduced risk of coronary heart disease (CHD). 1 Therefore, some physicians recommend moderate wine consumption to patients with adverse cardiovascular risk factors. 2 However, these are the same individuals at increased risk for developing nonalcoholic fatty liver disease (NAFLD). 3,4 NAFLD is closely related to metabolic syndrome and therefore shares many risk factors with CHD. Although the threshold for alcoholic liver disease is thought to be ingestion of 20 g to 30 g of alcohol per day for men and 10 g to 30 g of alcohol per day for women, 5,6 the threshold may be lower for overweight subjects who are at risk for both CHD and NAFLD. 7 The threshold for patients with pre-existing liver disease is unclear. The usual recommendation for patients with NAFLD is to strictly avoid alcohol. Despite the potential for liver injury, there is indirect evidence to suggest that modest wine and alcohol may by protective against liver injury. In an animal model, the wine polyphenol, resveratrol, reduces steatosis in mice fed with a high calorie diet. 8 Wine ameliorates many risk factors common to NAFLD and CHD such as insulin resistance and dyslipidemia. [9][10][11] These studies raise the possibility that wine may actually be protective against NAFLD. In the absence of concrete evidence, any recommendation regarding wine consumption in people at risk for both CHD and NAFLD remains controversial. Therefore,