AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis. METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites; engulfing RBCs found in stool were enrolled in the study. Regimen 1 included metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days. Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1. Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4. Student's t-test, chi(2) and McNemar's tests were used for statistical analysis. RESULTS: Three patients refused to participate. The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27 patients). The two groups were similar regarding their age, sex and clinical manifestations. In Group 1, diarrhea lasted 48.0+/-18.5 hours and in Group 2, 12.0+/-3.7 hours (P<0.0001). In Group 1, the durations of fever and abdominal pain were 24.0+/-8.8 and 24.0+/-7.3 hours and in Group 2 they were 12.0+/-5.3 and 12.0+/-3.2 hours, respectively (P<0.001). Duration of headache was similar in both groups. At week 4, amebic cysts were detected in 5 cases (18.5%) of Group 1 but in none of the Group 2 (P<0.02). CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage.