Fatty liver disease may interfere with liver regeneration and is postulated to result in an adverse outcome for patients subjected to partial hepatectomy. This study examines the impact of steatosis on outcome following hepatic resection for neoplasms. All patients with fatty livers (n=325) who underwent hepatectomy between December 1991 and September 2001 were identified from a prospective database. Slides were reviewed and steatosis was quantified as follows: <30% (mild) and > or =30% (marked). Patient data were gathered and compared with results in 160 control patients with normal livers; subjects were matched for age, comorbidity, and extent of liver resection. There were 223 patients with mild and 102 with marked steatosis. Those with steatosis were more likely to be men (59% marked vs. 55% mild vs. 43% control; P=0.01) with a higher body mass index (29.7+/-5.5 marked vs. 28.2+/-5.5 mild vs. 26.0+/-5.4 control; P<0.01), and treated preoperatively with chemotherapy (66% marked vs. 55% mild vs. 38% control; P<0.01). Total (62%, 48%, and 35%; P<0.01) and infective (43%, 24%, and 14%; P<0.01) complications correlated with the degree of steatosis. No difference was observed in complications requiring major medical intervention, hospitalization, or admission to the intensive care unit between groups. On multivariate analysis, steatosis was an independent predictor of complications (P<0.01, risk ratio=3.04, 95% confidence interval=1.7 to 5.54). There was a nonsignificant trend toward higher 60-day mortality in patients with marked steatosis who had lobe or more resections (9.4% marked vs. 5.0% mild vs. 5.0% control; P=0.30). Marked steatosis is an independent predictor of complications following hepatic resection but does not have a significant impact on 60-day mortality. Steatosis alone should not preclude aggressive hepatic resection for neoplasms when indicated; however, patients with marked steatosis undergoing large resections should still be approached with due caution.