A prospective prevalence study of Chlamydia trachomatis infection was conducted among adolescents experiencing school, family, and/or social difficulties at the Youth Health Center of Hôtel-Dieu Hospital in Paris. Epidemiological, clinical, and laboratory data were collected to identify factors associated with the infection. Over the course of one year (April 2006–2007), 356 patients were screened, with a prevalence of 16.1% among girls and 2.6% among boys. Among girls, the logistic regression analysis revealed that the factors most strongly associated with infection were: somatic complaints and having more than one sexual partner from the onset of sexual activity. The risk of infection increases with the age of the patient at the time of first sexual intercourse. Half of the infected patients were asymptomatic, and 10% of asymptomatic patients were infected. Treatment with doxycycline or azithromycin was offered to symptomatic or asymptomatic patients, respectively. Post-treatment follow-up was positive in 11% of patients, with 42% lost to follow-up. In this population, we recommend offering routine screening for C. trachomatis from the onset of sexual activity, repeating this screening in both infected and uninfected patients twice a year—including after confirmation of eradication—and educating patients on the proper use of condoms. (R.A.)