Background &amp; aims <p>Evidence regarding the mortality risk associated with cardiometabolic risk factors (CMRFs) in patients with metabolic dysfunction- associated steatotic liver disease (MASLD) remains limited. We aimed to explore the association between CMRFs and mortality and to develop a practical risk stratification method for patients with MASLD.</p> Patients and methods <p>MASLD patients from the National Health and Nutrition Examination Survey (NHANES III) database were included as the evaluation cohort, while NHANES 2003–2018 served as the validation cohort. The observational endpoints of the current study were all-cause and cardiac-specific mortality. Univariate and multivariate Cox proportional hazards regression models were employed to investigate the association of CMRFs with long-term mortality.</p> Results <p>A total of 3,545 MASLD patients were included in the evaluation cohort. During a median follow-up period of 26 years, 1,344 subjects died, of whom 347 deaths were attributable to cardiac-specific causes. Multivariate Cox regression models revealed elevated glucose and hypertension as significant predictors for both all-cause and cardiac-specific mortality. Based on the type and number of CMRFs, we stratified the MASLD patients into three risk groups. After risk stratification, the cumulative incidence of all-cause and cardiac-specific mortality at 20 years was 11.5% and 2.6% in the low-risk group, 25.5% and 9.3% in the medium-risk group, and 44.2% and 16.0% in the high-risk group, respectively. Sensitivity analysis and the validation cohort yielded similar findings.</p> Conclusions <p>Based on the type and number of CMRFs, we developed a practical risk stratification method for MASLD patients, enabling clinicians to identify patients at higher mortality risk and tailor follow-up and intervention plans accordingly.</p> Clinical trial registration <p>Not applicable.</p>