SummaryBackgroundMagnetic resonance imaging‐proton density fat fraction (MRI‐PDFF) is an excellent biomarker for the non‐invasive quantification of hepatic steatosis.AimTo examine clinical and histologic factors associated with discordance between steatosis grade determined by histology and MRI‐PDFF in patients with non‐alcoholic fatty liver disease (NAFLD)MethodsWe included 728 patients with biopsy‐proven NAFLD from UC San Diego (n = 414) and Yokohama City University (n = 314) who underwent MRI‐PDFF and liver biopsy. Patients were stratified by steatosis, and matched with MRI‐PDFF cut‐points for each steatosis grade: 0 (MRI‐PDFF < 6.4%), 1 (MRI‐PDFF: 6.4%–17.4%), 2 (MRI‐PDFF: 17.4%–22.1%), 3 (MRI‐PDFF ≥ 22.1%). Primary outcome was major discordance defined as ≥2 steatosis grade difference determined by histology and MRI‐PDFF.ResultsMean (±SD) age and BMI were 55.3 (±13.8) years and 29.9 (±4.9) kg/m², respectively. The distributions of histology and MRI‐PDFF‐determined steatosis were 5.5% grade 0 (n = 40), 44.8% 1 (n = 326, 44.8%), 33.9% 2 (n = 247), and 15.8% 3 (n = 115) vs. 23.5% grade 0 (n = 171), 49.7% 1 (n = 362), 12.9% 2 (n = 94), and 13.9% 3 (n = 101). Major discordance rate was 6.6% (n = 48). Most cases with major discordance had greater histology‐determined steatosis grade (n = 40, 88.3%), higher serum AST and liver stiffness, and greater likelihood of fibrosis ≥2, ballooning ≥1 and lobular inflammation ≥2 (all p < 0.05).ConclusionHistology overestimates steatosis grade compared to MRI‐PDFF. Patients with advanced NASH are likely to be upgraded on steatosis grade by histology. These data have important implications for steatosis estimation and reporting on histology in clinical practice and trials, especially in patients with stage 2 fibrosis.