Background <p>Cardiometabolic Index (CMI) is positively correlated with liver fibrosis in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), but its association with mortality risk in MASLD patients remains unclear.</p> Methods <p>This study utilized data from NHANES III and linked it with the mortality database up to December 31, 2019. Cox regression analysis was used to examine the relationship between CMI and mortality rates. Linear regression analysis was conducted to explore the correlation between CMI and the TyG index, and mediation analysis was performed to investigate the potential mechanisms underlying the association between CMI and mortality.</p> Results <p>The study included 2,260 MASLD patients with a median age of 51 years and a median CMI of 2.5. In the fully adjusted Cox regression model, CMI was positively associated with all-cause mortality (per 1-SD increase, HR = 1.04, 95% CI = 1.00-1.08) and other-cause mortality rates (per 1-SD increase, HR = 1.25, 95% CI = 1.12–1.40), but not with cardiovascular or cancer-related mortality. Mediation analysis indicated that the TyG index mediated 16.6% of the association between CMI and all-cause mortality.</p> Conclusion <p>CMI in MASLD patients is associated with an increased risk of all-cause and other-cause mortality.</p>