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Metronidazole-resistant Trichomonas vaginalis has been reported across the United States. Some reports have suggested that clinically resistant cases could be increasing. Currently, metronidazole is the only drug available to treat trichomoniasis, including resistant cases. In such cases, treatment usually consists of giving higher and more prolonged doses of metronidazole, which patients are often unable to tolerate. Tinidazole, a second-generation nitroimidazole currently under development in the United States, has been shown to be an effective therapy in resistant T. vaginalis. Tinidazole appears to have several advantages over metronidazole, including greater in vitro potency against both sensitive and resistant strains of T. vaginalis, a more prolonged duration of action, and improved patient tolerability. This report describes the successful use of tinidazole in 3 cases of clinically metronidazole-resistant trichomoniasis.