Objective: To assess the incidence, cofactors, and excess risk of development of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis, attributable to tamoxifen in women. Design: Prospective, randomised, double bli nd, placebo controlled trial. Setting and par ticipants: 5408 healthy women who had had hysterectomies recruited into the It alian tamoxifen chemoprevention trial from 58 centres in Italy. Intervention: Wo men were randomly assigned to receive tamoxifen (20 mg daily) or placebo for fiv e years. Main outcome measure: Development of nonalcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevat ions of alanine aminotransferase (≥1.5 times upper limit of normal) over a six month period. Results: During follow up, 64 women met the predefined criteria: 1 2 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed nonalcoholic fatty liver disease (34 tamoxifen, 18 placebo) hazard ratio = 2.0 (95%confidence interval 1.1 to 3.5; P=0.04). In all 52 wom en ultrasonography confirmed the presence of fatty liver. Other factors associat ed with the development of nonalcoholic fatty liver disease.ticipants:5408healthy w recruited into the Italian Objective: To assess the incidence, cofactors, and excess risk of development of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis, attributable to tamoxifen in women. Design: Prospective, randomized, double bli nd, placebo controlled trial. par ticipants: 5408 healthy women who had hysterectomies recruited into the It alian tamoxifen chemoprevention trial from 58 centers in Italy. Intervention: Wo men were randomly assigned to receive tamoxifen (20 mg daily) or placebo for fiv e years. Main outcome measure: Development of nonalcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (≧ 1.5 times upper limit of normal) over a six month period. Results: During follow up, 64 women met the selected criteria: 1 2 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo) hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 wom en ultrasonography confirmed the presence of fatty liver. Other factors associat ed with the development of nonalcoholic fatty liver disease. ticipants: 5408healthy w recruited into the Italian