Metronidazole resistance is an uncommon cause of treatment failure of Trichomonas vaginalis. High-dose intravenous metronidazole was used successfully to treat a patient in whom repeated oral therapy with this agent had failed. Metronidazole resistance was documented by aerobic cultures for susceptibility; anaerobic cultures failed to indicate resistance. Metronidazole serum levels were documented. With failure of repeated oral therapy, intravenous metronidazole may be indicated if there is no evidence of other causes for treatment failure, such as patient noncompliance or reinfection.