BACKGROUND Trichomonas vaginalis is the causative agent of the most common curable sexually transmitted disease in the world. The infection is treated with a single oral dose of metronidazole or tinidazole, currently the only licensed class of drugs available for this indication; however, both of these antimicrobials are associated with significant gastrointestinal adverse effects, and some individuals are unable to tolerate them because of these adverse effects. METHODS Randomized, dose-ranging pilot study conducted in 2 phases consisting of 20 participants in each phase. In the first phase, participants were randomized to the vaginal suppository (metronidazole 750 mg/miconazole nitrate 200 mg) twice a day for 7 days versus oral metronidazole 2 g single dose. In the second phase, participants randomized to suppository used it once a day for 7 days. Women were reevaluated on days 12 to 15 and 30 to 35. Treatment failures were defined as persistence of trichomonas by wet prep and/or culture. RESULTS There were no significant differences in cure rates between the vaginal suppositories and oral metronidazole in either phase. The overall efficacy across both follow-up visits was 80% versus 90% for the suppository (2×/d) versus oral medication arms in phase 1 (P = 1.00) and 78% versus 70% for the suppository (1×/d) versus oral medication arms in phase 2 (P = 1.00). The results were also nonsignificant when combining results across arm (P = 1.00). CONCLUSIONS High-dose intravaginal metronidazole combined with miconazole offers the possibility of a well-tolerated treatment that avoids the systemic adverse effects of nitroimidazoles for the treatment of trichomoniasis.