Background. Trichomonas vaginalis infection is a sexually transmitted infection (STI) linked with reproductive health complications. However, few data exist concerning the epidemiologic profile of this pathogen in adolescent women, a group at high risk for other STIs. Methods. Our objective was to describe the prevalence, incidence, natural history, and response to treatment of T. vaginalis infection in adolescent women. Women 14-17 years old were followed for up to 27 months. Vaginal swab samples were obtained during quarterly clinic visits and were self-obtained weekly during 12-week diary collection periods. The weekly samples were tested quarterly. Infections were identified by polymerase chain reaction and were treated with 2.0 g of oral metronidazole. Analysis was performed on the subset of participants who returned for at least 1 quarterly clinic visit. Results. T. vaginalis infection was identified in 6.0% (16/268) of the participants at enrollment. Overall, 23.2% (57/245) of the participants with at least 3 months of follow-up had at least 1 infection episode; 31.6% (18/57) experienced multiple episodes. Seventy-two incident infection episodes were diagnosed. When treatment was not documented, weekly samples from participants were positive for up to 12 consecutive weeks. After treatment, T. vaginalis DNA was undetectable within 2 weeks in all but 3 participants. Conclusions. The incidence of T. vaginalis infection is high among adolescent women; untreated infections may last undetected for 3 months or longer. Reinfection is common. Treatment with oral metronidazole is effective, and T. vaginalis DNA disappears rapidly after treatment. © 2005 by the Infectious Diseases Society of America. All rights reserved.