ABSTRACT: Alcohol use is a leading risk factor for the global disease burden including liver diseases. However, the combined effect of alcohol use and body mass index (BMI) on alcohol-related diseases has seldom been examined. We examined whether alcohol consumption and BMI could act together to increase mortality from nonneoplastic liver diseases, upper aero-digestive tract (UADT) cancers, and alcohol use disorders (AUD) in middle-aged Korean men.107,735 men (mean age, 58.8 years) participated in a postal survey in 2004 and were followed until 2010, by linkage to national death records. Hazard ratios (HRs) of cause-specific death were calculated after adjustment for confounders.Each 5-drink (approximately 45 g alcohol) higher weekly alcohol consumption was associated with increased mortality, by approximately 70% for nonneoplastic liver disease mortality (HR = 1.70, P < 0.001), approximately 60% for UADT cancer mortality (HR = 1.64, P < 0.001), and approximately 70% for AUD mortality (HR = 1.71, P < 0.001). Generally, BMI was inversely associated with these alcohol-related diseases (HR per each 5 kg/m higher BMI = 0.18-0.46, P < 0.001 for each cause), while, in participants with BMI ≥25 kg/m, each 5 kg/m higher BMI was also associated with an elevated mortality from nonneoplastic liver diseases of approximately 150% (HR = 2.52, P = 0.001). Men with BMI < 21 kg/m and weekly alcohol consumption ≥14 drinks showed markedly higher mortality from nonneoplastic liver diseases (HR = 5.7), alcoholic liver diseases (HR = 9.3), UADT cancers (HR = 10.5), and esophageal cancer (HR = 15.5), compared to men drinking less than 1 drink/wk with BMI ≥25 kg/m. The combined effect of low BMI and high weekly alcohol consumption was 2.25- to 3.29-fold greater than the additive effect of each factor for these alcohol-related diseases (P < 0.05 for each cause).Alcohol consumption and low BMI were related to deaths from nonneoplastic liver diseases, UADT cancers, and AUD, with evidence of a supra-additive combined effect of both factors. High BMI was also related to deaths from nonneoplastic liver diseases. Men with a low BMI (<23 kg/m) are suggested to be prone to the harmful effects of alcohol.