Tumor necrosis factor‐α (TNF‐α) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2‐month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score ≥32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% ± 11%) than in group B (18% ± 9%). The study was stopped by the follow‐up committee and the sponsor (Assistance Publique‐Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P < .002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections. (HEPATOLOGY 2004;39:1390–1397.)