Background and Aims: There is limited evidence about the association of healthy lifestyle and all-cause mortality in individuals with metabolic associated fatty liver disease (MAFLD). We aimed to examine this association and compare it with the association in those without MAFLD. Methods: A prospective cohort study was performed and linked mortality data through 2019 in the National Health Nutrition Examination Survey (NHANES 1999–2010). A healthy lifestyle score was constructed from cigarette smoking, alcohol drinking, healthy eating score, and leisure-time physical activity. Risk stratification was conducted in participants with MAFLD by fibrosis biomarkers and liver enzymes. Survey-weight adjusted Cox regression was used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality associated with healthy lifestyle. Results: There was a protective association between healthy lifestyle and all-cause mortality in participants with MAFLD (HR per 1-unit increase of healthy lifestyle score 0.77 [95% CI 0.69–0.85]), with no difference from the association in participants without MAFLD (HR 0.77 [0.72–0.82]). In participants with MAFLD, the associations tended to be stronger in those with lower risk of advanced fibrosis (HR per 1-unit increase of healthy lifestyle score 0.64 [0.50–0.79] for low NAFLD fibrosis score [NFS] and 0.84 [0.75–0.93] for high NFS, p-value for interaction 0.02), but did not differ by liver enzymes. The results for non-alcoholic fatty liver disease (NAFLD) mirrored those for MAFLD. Conclusions: Healthy lifestyle showed protective associations with all-cause mortality regardless of MAFLD status, and the associations tended to be stronger in those with lower risk of advanced fibrosis. Timely lifestyle modification matters for individuals with MAFLD. [ABSTRACT FROM AUTHOR]