The use of enteral antibiotics to prevent acute graft versus host disease (GvHD) has not been studied prospectively in children. We hypothesized the risk of GvHD in pediatric bone marrow transplant (BMT) recipients would be decreased with enteral metronidazole. Eligible subjects included pediatric patients referred to one center for first allogeneic BMT. Enteral metronidazole 20 mg/kg/day divided thrice daily (maximum 750 mg/day) was administered from day− 14 to day+ 35. The risk of GvHD grade II or more severe among subjects treated with metronidazole was compared to historical controls. There were no significant differences between treated (n= 19) and historical controls (n= 83) with respect to age, gender, prophylaxis, or conditioning regimens, proportion receiving unrelated donor marrow, proportion receiving umbilical cord blood, or transplantation indication. The probability of remaining free of GvHD at day+ 100 was lower in the treated group (P= 0.047). The adjusted relative risk of developing GvHD among subjects treated with metronidazole was 0.36 (95% CI: 0.13–0.997; P= 0.05). Five patients were unable to complete the study; two were likely related to study medication. We conclude that enteral metronidazole appears effective in the prevention of GvHD. These results suggest that a randomized trial is justifiable in children, especially recipients of alternative donor BMT.