SummaryAimsA multi‐stakeholder consensus has proposed MASLD (metabolic dysfunction‐associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid‐term mortality of patients with biopsy‐proven MASLD in Japan.MethodsWe enrolled 1349 patients with biopsy‐proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data‐mining analysis.ResultsThe prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty‐five patients with MASLD died. Of these, liver‐related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9‐fold and 1.8‐fold risk of mortality, respectively. In the decision‐tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid‐term prognosis of patients with MASLD.ConclusionsIn patients with biopsy‐proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver‐related events. Hepatic inflammation and fibrosis were significant factors influencing mid‐term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.