Objective <p>The objective of this study was to validate the diagnostic accuracy of the acFibroMASH index in a population of metabolic dysfunction-associated steatotic liver disease (MASLD) patients with at-risk metabolic dysfunction-associated steatohepatitis (MASH) and to compare it with other scoring systems.</p> Methods <p>394 patients with biopsy-proven MASLD were retrospectively enrolled. The patients were divided into the at-risk MASH (NAFLD activity score ≥ 4 and significant fibrosis) group (<i>n</i> = 103) and the non-at-risk MASH group (<i>n</i> = 291). The diagnostic performance of the acFibroMASH index was compared to that of fibroScan-aspartate aminotransferase (FAST) and other noninvasive fibrosis scores by plotting the receiver operating characteristic curve (ROC), including the area under the curve (AUC), sensitivity, and specificity. Cut-offs of the acFibroMASH index for sensitivity (≥ 0.90) and specificity (≥ 0.90) were obtained in our cohort.</p> Results <p>The AUC of the acFibroMASH index in assessing at-risk MASH was 0.780, while the AUC of FAST was 0.770. The comparison of acFibroMASH with FAST showed no significant difference (<i>P</i> = 0.542). When the cut-off value for acFibroMASH was &lt; 0.15, 95.5% of at-risk MASH patients could be excluded in 89 patients correctly. Conversely, when the cut-off value was set at &gt; 0.39, 49.3% of at-risk MASH patients could be diagnosed in 140 patients correctly. When the NPV was set at 0.900, the critical value for exclusion was determined to be 0.23, with a sensitivity of 0.835 and a specificity of 0.526.</p> Conclusion <p>This study validated the efficacy of the acFibroMASH index in predicting at-risk MASH in a population of MASLD patients, demonstrating comparable performance to that of the FAST. The acFibroMASH index may provide a valuable clinical basis for screening and identifying at-risk MASH in primary care settings.</p>