Non-alcoholic fatty liver disease (NAFLD) could play a catalyst role on the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy NAFLD patients remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension (AHT), and dyslipidemia) in metabolically healthy patients.From HEPAmet Registry (N=1030), we included 178 biopsy-proven NAFLD patients with a metabolically healthy status, defined by the absence of baseline T2DM, AHT, and dyslipidemia. Hepamet Fibrosis Score (HFS), NAFLD Fibrosis Score, and FIB-4 were calculated. Follow-up was computed from the biopsy to the diagnosis of T2DM, AHT, or dyslipidemia.During a follow-up of 5.6+4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis [HR 2.95 (CI95% 1.19-7.31); p=0.019], glucose levels [p=0.008], age [p=0.007] and BMI [p=0.039]. AHT was independently linked to significant fibrosis [HR 2.39 (CI95% 1.14-5.10); p=0.028], age [p=0.0001], BMI [p=0.006], glucose [p=0.021] and platelets [p=0.050]. The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in presence of obesity, similar than AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% (4/16) vs. HFS <0.12 4.5% (4/88); logRank 6.658, p=0.010).Metabolically healthy patients with NAFLD-related significant fibrosis were at higher risk for the development of T2DM and AHT. HFS>0.12, but not FIB4 or NFS predicted the occurrence of T2DM.