An increase in intestinal gas production due to small intestinal bowel overgrowth (SIBO) is a contributing factor for flatus incontinence. The aims of our study were to assess the efficacy of metronidazole in a select population of patients with flatus incontinence associated with SIBO and to compare its efficacy with that of a combination of simethicone and activated charcoal (SC; Carbosylane) in randomized experimental arms. Adult patients suffering from flatus incontinence associated with SIBO diagnosed by a glucose breath test were enrolled in the study. They were given metronidazole or Carbosylane (SC) for 10 days. The reduction in the mean daily number of gas leakages reported in a 3-day diary before and at the end of the treatment was used as the primary endpoint. Of 52 consecutive subjects with flatus incontinence, 23 (44%) had SIBO, 16 (33%) of whom were included in and completed the study. The relative reduction in flatus incontinence episodes was significantly higher in the metronidazole than in the SC group (66.8±34.8% vs. 25±50%, P = 0.03), decreasing by more than 50% in 7 (87.5%) of the subjects in the metronidazole group compared with only 1 (12.5%) in the SC group (odds ratio 1.9, 95% confidence interval 0.9-56.9, P = 0.06). Our results show a promising trend indicating that metronidazole might significantly improve flatus incontinence associated with SIBO and might be more successful in treating flatus incontinence than gas absorbents.