BACKGROUND: The results of the addition of gemtuzumab ozogamicin, an anti-CD33 antibody conjugate, to the standard treatment for patients with acute myeloid leukaemia in phase 3 trials were contradictory. We investigated whether the addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line chemotherapy would improve the outcome of patients with this leukaemia without causing excessive toxicity. METHODS: In a phase 3, open-label study, undertaken in 26 haematology centres in France, patients aged 50-70 years with previously untreated de novo acute myeloid leukaemia were randomly assigned with a computer-generated sequence in a 1:1 ratio with block sizes of four to standard treatment (control group) with or without five doses of intravenous gemtuzumab ozogamicin (3 mg/m(2) on days 1, 4, and 7 during induction and day 1 of each of the two consolidation chemotherapy courses). The primary endpoint was event-free survival (EFS). Secondary endpoints were relapse-free (RFS), overall survival (OS), and safety. Analysis was by intention to treat. This study is registered with EudraCT, number 2007-002933-36. FINDINGS: 280 patients were randomly assigned to the control (n=140) and gemtuzumab ozogamicin groups (n=140), and 139 patients were analysed in each group. Complete response with or without incomplete platelet recovery to induction was 104 (75%) in the control group and 113 (81%) in the gemtuzumab ozogamicin group (odds ratio 1*46, 95% CI 0*20-2*59; p=0*25). At 2 years, EFS was estimated as 17*1% (10*8-27*1) in the control group versus 40*8% (32*8-50*8) in the gemtuzumab ozogamicin group (hazard ratio 0*58, 0*43-0*78; p=0*0003), OS 41*9% (33*1-53*1) versus 53*2% (44*6-63*5), respectively (0*69, 0*49-0*98; p=0*0368), and RFS 22*7% (14*5-35*7) versus 50*3% (41*0-61*6), respectively (0*52, 0*36-0*75; p=0*0003). Haematological toxicity, particularly persistent thrombocytopenia, was more common in the gemtuzumab ozogamicin group than in the control group (22 [16%] vs 4 [3%]; p