BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD. OBJECTIVE To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS. METHODS A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of "Non-Alcoholic fatty liver disease" using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. RESULTS Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33). CONCLUSIONS Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.