The aim of this cross-sectional study was to present nationally representative findings on the co-occurrence of obesity and specific patterns of alcohol use associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gammaglutamyltransferase (GGT) among adults in the United States. We analyzed data from 8,373 adults aged >= 20 years who participated in the 2005-2008 National Health and Nutrition Examination Survey. We produced prevalence ratios by using the co-occurrence of obesity (i.e., body mass index >= 30.0 kg/m(2) or waist circumference >= 102 cm in men and >= 88 cm in women) and specific patterns of alcohol use (i.e., non-drinkers, non-excessive drinkers, and excessive drinkers) as a predictor; elevations in serum ALT, AST, and GGT were used as an outcome variable while adjusting for covariates in multivariate regression models. Approximately 34.7% of adult men and 38.6% of adult women in the United States had co-occurrence of obesity and any alcohol use, including 16.4% of men and 9.8% of women who had co-occurrence of obesity and excessive drinking during 2005-2008. When compared to male non-drinkers without obesity after multivariate adjustment, male excessive drinkers with obesity were 3.08 (95% CI: 1.80-5.28), 2.42 (95% CI: 1.80-3.26), and 3.15 (95% CI: 1.82-5.46) times more likely to exhibit elevated serum ALT, AST, and GGT, respectively. Similarly, when compared to female nondrinkers without obesity, female excessive drinkers with obesity were 2.36 (95% CI: 1.38-4.04), 3.27 (95% CI: 1.85-5.78), and 3.43 (95% CI: 2.19-5.40) times more likely to have elevated serum ALT, AST, and GGT, respectively. The co-occurrence of obesity and excessive drinking may place adults at an increased risk for potential liver injury. Our study findings provide support for evidence-based clinical and population-based interventions that integrate health behavior change among adults who have these co-occurring risk factors.