OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be positively associated with serum advanced glycation end products (AGEs) and negatively with soluble receptor for AGE (sRAGE) in a few small studies. We aimed to test the association between lifestyle and sRAGE levels and the association between sRAGE levels or AGEs intake and NAFLD, insulin resistance (IR), and elevated alanine aminotransferase (ALT). METHODS: Cross-sectional analysis among participants of a screening study. Fasting blood tests and serum sRAGE levels were obtained. NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment, respectively. Nutritional intake was measured by food frequency questionnaire, and the intake of dietary AGEs was calculated. RESULTS: A total of 743 subjects were included (52.6% men, mean age 58.83 ± 6.58 years, 38.7% NAFLD). Exercise was independently protective from low sRAGE levels (odds ratio [OR]=0.71,95%confidence interval 0.52–0.97, P = 0.031). Pack-years, working time, and sedentary time (OR = 1.51, 1.03–2.22, P = 0.036; OR = 1.66, 1.18–2.35, P = 0.004; OR = 1.64, 1.18–2.29, P = 0.004, respectively), and intake of red and/or processed meat or processed meat alone (OR = 1.01, 1.04–2.21, P = 0.045; OR = 1.49, 1.00–2.21, P = 0.048, respectively) were associated with increased odds for low sRAGE levels. Low sRAGE levels were independently associated with elevated ALT (OR=1.69, 1.11–2.57, P=0.014) and NAFLD with elevated ALT (OR=2.17, 1.23–3.83, P= 0.007). High intake of dietary AGEs was associated with IR (OR = 2.04, 1.25–3.34 P = 0.004). DISCUSSION: Lifestyle is associated with sRAGE levels and, in turn, low levels of sRAGE are associated with NAFLD and elevated ALT.