It has been suggested that hepatitis C virus (HCV) and especially genotype 3 is associated with steatosis. We assess the effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis. We analyzed 1,428 naïve patients included in a randomized trial. A single pathologist scored steatosis at baseline and 24 weeks after the treatment. At baseline, steatosis was present in 935 of 1,428 patients (65%), including 175 (83%) of 210 patients with genotype 3 versus 760 (62%) of 1,218 with other genotypes (P < .001). The variables associated with steatosis in logistic regression were genotype 3 (P < .001), triglycerides greater than 1.7 mmol/L (P < .001), body mass index greater than 27 (P < .04), age greater than 40 years (P < .001), and septal fibrosis (P = .007). In genotype 3-infected patients, steatosis was associated with high viral load and with lower serum cholesterol. Steatosis was associated with lower sustained response rate, even after taking into account other factors (P < .001). Among virologic responders, steatosis was much improved in genotype 3, improvement of at least 1 grade in 77%, and disappearance in 46% compared with other genotypes, 46% and 29%, respectively (P < .001 both comparisons). In genotype 3 responders, the baseline low serum cholesterol was corrected by treatment (P < .001). Steatosis was associated with HCV genotype 3, triglycerides, high body mass index, age, fibrosis stage, and lower virologic response to treatment. In conclusion, sustained disappearance of the virus is associated with reduction of steatosis in genotype 3 as well as a correction of baseline low serum cholesterol.