Aldafermin, an engineered analog of FGF19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with non-alcoholic steatohepatitis (NASH).We performed a double-blind study of 78 patients with NASH at 9 centers in the United States. Key inclusion criteria were biopsy-proven NASH with non-alcoholic fatty liver disease activity score (NAS) ≥4, stage 2 or 3 fibrosis by NASH Clinical Research Network classification, and absolute liver fat content (LFC) ≥8%, measured by magnetic resonance imaging-proton density fat fraction. Patients were randomly assigned (1:2) to groups given subcutaneous placebo (n=25) or aldafermin 1 mg (n=53) daily for 24 weeks. The primary outcome was change in absolute LFC from baseline at week 24. Secondary outcomes included serum markers and histological measures of fibrosis improvement and NASH resolution.At week 24, the aldafermin group had a significant reduction in absolute LFC (reduction of 7.7%) compared with placebo (reduction of 2.7%; difference, reduction of 5.0%; 95% CI, reduction of 8.0%-1.9%; P = .002). Aldafermin produced significantly greater decreases in levels of 7alpha-hydroxy-4-cholesten-3-one, bile acids, alanine and aspartate aminotransferases, and Pro-C3 than placebo. Fibrosis improvement (≥1 stage) with no worsening of NASH was achieved in 38% of patients receiving aldafermin vs 18% of patients receiving placebo (P = .10). NASH resolution with no worsening of fibrosis was observed in 24% of patients given aldafermin vs 9% of patients given placebo (P = .20). Discontinuations due to adverse events occurred in no patients in the aldafermin group and 4% of patients in the placebo group.In a phase 2 trial of patients with NASH, aldafermin reduced liver fat and produced a trend toward fibrosis improvement. ClinicalTrials.gov no: NCT02443116.