The incidence of nonalcoholic fatty liver disease (NAFLD) is highest among Mexican-origin (MO) adults. Few studies have estimated the prevalence of NAFLD in this subpopulation, particularly by sex and age. We assessed the prevalence of NAFLD in a community sample of MO adults residing in a border region of southern Arizona and determined risk factors associated with NAFLD. A total of 307 MO adults (n = 194 women; n = 113 men) with overweight or obesity completed an in-person study visit, including vibration-controlled transient elastography (FibroScan) for the assessment of NAFLD status. A continuous attenuation parameter score of ≥288 dB/m (≥5% hepatic steatosis) indicated NAFLD status. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD. We identified 155 participants (50%) with NAFLD, including 52% of women and 48% of men; there were no sex differences in steatosis (men, 287.8 dB/m; women, 288.4 dB/m). Sex, age, patatin-like phospholipase domain containing 3 (PNPLA3) risk allele carrier status, comorbidities, and cultural and behavioral variables were not associated with NAFLD status. There was some evidence for effect modification of body mass index (BMI) by sex (P interaction = 0.08). The estimated OR for an increase in BMI of 5 kg/m 2 was 3.36 (95% CI, 1.90, 5.91) for men and 1.92 (95% CI, 1.40, 2.64) for women. In post hoc analyses treating steatosis as a continuous variable in a linear regression, significant effect modification was found for BMI by sex (P interaction = 0.03), age (P = 0.05), and PNPLA3 risk allele carrier status (P = 0.02). Conclusion: Lifestyle interventions to reduce body weight, with consideration of age and genetic risk status, are needed to stem the higher rates of NAFLD observed for MO populations. (Hepatology Communications 2022;6:1322-1335).N onalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome that is defined as steatosis affecting ≥5% of hepatocytes not caused by excess alcohol intake, hepatitis B or C, autoimmune hepatitis, iron overload, drugs, or toxins. (1)(2)(3) It is estimated to affect approximately 20% (64 million) of the United States (US) population each year, leading to annual medical costs exceeding $100 billion. (4) Although not all individuals with NAFLD progress to end-stage liver disease, nearly 30% are at greater risk for developing cirrhosis, portal hypertension, and hepatocellular carcinoma (HCC), making NAFLD an emerging risk factor for HCC that is projected to become the leading cause of