Fibrosis is an independent predictor of death in NASH. We assessed the associations between histologic and non-invasive (NITs) fibrosis tests with clinical and patient-reported outcomes (PROs) in advanced NASH.Patients with advanced NASH (NASH CRN stage F3 or F4) were enrolled in four multinational clinical trials of simtuzumab and selonsertib. Liver biopsies, NITs, and PROs (SF-36, CLDQ-NASH, EQ-5D, WPAI) were prospectively collected.2154 patients with advanced NASH were included: 52.5% F4, 40% male, 72% type 2 diabetes, baseline liver stiffness 24.1±14.2 kPa in F4, 14.6 ± 8.0 kPa in F3, baseline mean ELF score 11.4±1.2 in F4, 10.3±1.0 in F3; median follow-up16 months. Of those with baseline F3, 16.7% experienced disease progression to cirrhosis while those with F4, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NITs (all p<0.0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both F3 and F4 groups (p<0.01 for all NITs in F3; for ELF, NAFLD Fibrosis Score (NFS), FIB-4, liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF ≥10.43, NFS ≥ 1.80, Fibrotest ≥ 0.54, liver stiffness ≥ 23.4 kPa. During treatment, patients with decreases in NITs experienced improvement of their PRO scores while those with increase in NITs had their PRO scores worsened (p<0.05).Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH.