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Studies on aspirin’s effects on metabolic-associated fatty liver disease (MAFLD) are limited. The aim of this study was to assess the association between aspirin and all-cause and cardiovascular disease (CVD) mortality in individuals with MAFLD. Data were acquired from the National Health And Nutrition Examination Survey (NHANES) III. MAFLD diagnosis was consistent with that of international expert consensus. The independent association between aspirin and all-cause and CVD mortality in participants with MAFLD was evaluated by multiple Cox regression. Stratified analyses and interaction tests were performed to investigate whether covariates modified the association between aspirin and MAFLD mortality. Of 4594 eligible participants, 3,162 (68.83%) never took aspirin (0 times/month), 962 (20.94%) took it occasionally (1–14 times/month) and 470 (10.23%) took it regularly (≥15 times/month). Multiple cox regression showed that aspirin was not associated with overall mortality for MAFLD individuals. Stratified analysis revealed that in middle-aged (45–59 years) participants with MAFLD, occasional aspirin use was associated with low all-cause mortality risk (HR = 0.61, 95% CI = 0.43–0.86), while there was no significant association between aspirin and all-cause mortality among the young or the elderly. We found that the association between aspirin and all-cause MAFLD mortality varies by both age and frequency of administration. More prospective studies are needed to explore aspirin’s influence on MALFD mortality.

Association of aspirin with all-cause and cardiocerebrovascular mortality in patients with metabolic associated fatty liver disease