Recent reports of the pathogenic potential of Dientamoeba fragilis have underlined the need for an effective treatment against this colon-dwelling protozoan. Metronidazole is a well-known and commonly used anti-protozoal agent, but another 5-nitroimidazole derivative, ornidazole, may be preferable, where available, because of its longer half-life and fewer side-effects. This study compared the efficacies of metronidazole and ornidazole in a group of 112 patients with dientamoebiasis. Patients were randomised into two treatment groups: group 1 (n = 56) received metronidazole for 5 days, 20 mg/kg/day for children and 1.5 g/day for adults, in three oral doses, while group 2 (n = 56) received a single oral dose of ornidazole, 30 mg/kg for children and 2 g for adults. Stool samples were examined on the seventh and 14th days after treatment, and clinical symptoms were recorded to evaluate the efficacy of treatment. A statistically significant difference was recorded between the efficacies of ornidazole and metronidazole, both parasitologically (92.9% vs. 69.6%, p 0.001) and clinically (96.4% vs. 76.8%, p 0.001). Patients in the metronidazole group reported more side-effects than patients in the ornidazole group, none of whom required termination of treatment. These results suggest that single-dose ornidazole may be an important alternative agent for the treatment of dientamoebiasis.