Despite the high prevalence of fatty liver disease, the safety of liver resection in settings of steatohepatitis (SH) or hepatic steatosis is poorly understood. The aim of this study was to determine whether underlying SH or simple hepatic steatosis increases morbidity after liver resection. We compared patients undergoing liver resection with underlying SH or greater than 33% simple hepatic steatosis to controls selected for similar demographics, diagnoses, comorbidities, preoperative chemotherapy treatments, and extent of partial hepatectomy. Primary endpoints included postoperative overall and hepatic-related morbidity. One hundred and two patients with SH and 72 with greater than 33% simple hepatic steatosis who underwent liver resection from 2000 to 2011 were compared to corresponding controls. There were no differences in extent or approach of liver resection, malignant indications, preoperative chemotherapy treatment, elements of metabolic syndrome, alcohol use history, American Society of Anesthesiologists score, age, or gender between patients with SH or simple steatosis and corresponding controls. Ninety-day postoperative overall morbidity (56.9% versus 37.3%; P = 0.008), any hepatic-related morbidity (28.4% versus 15.7%; P = 0.043), surgical hepatic complications (19.6% versus 8.8%; P = 0.046), and hepatic decompensation (16.7% versus 6.9%; P = 0.049) were greater among SH patients, compared to corresponding controls. In contrast, there were no differences in postoperative overall morbidity (34.7% versus 44.4%; P = 0.310), any hepatic-related morbidity (19.4% versus 19.4%; P = 1.000), surgical hepatic complications (13.9% versus 9.7%; P = 0.606), or hepatic decompensation (8.3% versus 9.7%; P = 0.778) between simple hepatic steatosis patients and corresponding controls. Using multivariable logistic regression, SH was independently associated with postoperative overall (odds ratio [OR], 2.316; 95% confidence interval [95% CI]: 1.267-4.241; P = 0.007) and any hepatic-related (OR, 2.722; 95% CI: 1.201-6.168; P = 0.016) morbidity. Conclusion: Underlying SH, but not simple hepatic steatosis, increases overall and hepatic-related morbidity after liver resection. (HEPATOLOGY 2012)