Background and Aim <p>Angiogenesis is considered a vital mechanism of metabolic dysfunction-associated steatotic liver disease (MASLD), while angiopoietin-1 (ANGPT1) is a crucial regulatory factor of angiogenesis. However, whether circulating ANGPT1 level is related to MASLD remains unclear.</p> Methods <p>To conduct this cross-sectional study, adults who underwent their annual health examinations at the First Affiliated Hospital of Zhejiang University during January, 2024 to March, 2024 were enrolled. Anthropometric and biochemical parameters were measured. Mann–Whitney U test, chi-squared (χ2) test, Spearman’s analysis, step-wise univariate and multivariate logistic regression were used to analyze the role of ANGPT1 in MASLD.</p> Results <p>A total of 169 MASLD patients and 204 non-MASLD controls were enrolled. MASLD patients had significantly higher serum level of ANGPT1 than non-MASLD controls (44.37(36.86–50.43) versus 35.17(26.10-43.89), ng/ml, <i>P</i> &lt; 0.001). Serum ANGPT1 levels were positively related to the prevalence of MASLD (from 5.71% in the first quartile, to 37.32%, 53.71%, 95.24% in the second, third, and fourth quartiles, respectively, P_trend &lt; 0.001). Both univariate and multivariate stepwise logistic regression show positive correlation between ANGPT1 and MASLD (odds ratio (OR) 1.088, 95% confidence interval (CI) 1.063–1.113, <i>P</i> &lt; 0.001; adjusted OR 1.084, 95% CI 1.038–1.133, <i>P</i> &lt; 0.001, respectively). These positive correlations remain significant in different subgroups of age, gender, w/o obese or hyperglycemia (adjusted OR 1.031–1.172, all <i>P</i> &lt; 0.01).</p> Conclusions <p>This study revealed a positive association between serum ANGPT1 and MASLD, suggesting its potential as both a diagnostic and a therapeutic target.</p>