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Chlamydia trachomatis infections can lead to serious and costly sequelae. Because chlamydia is most often asymptomatic, many infected youth do not seek testing. Entry to a detention system provides an opportunity to screen and treat many at-risk youth.The goal of this study was to determine the cost-effectiveness of screening male youth for chlamydia on entry to detention.Incremental cost-effectiveness of 3 chlamydia screening strategies was compared for a hypothetical cohort of 4000 male youth per year: 1) universal chlamydia screening using a urine-based nucleic acid amplification test (NAAT), 2) selective NAAT screening of urine leukocyte esterase (LE)-positive urines, and 3) no screening. The model incorporated programmatic costs of screening and treatment and medical cost savings from sequelae prevented in infected males and female partners. The analysis was conducted from the healthcare system perspective.Chlamydia prevalence in the sampled population of 594 was 4.8%, and the average number of female sexual partners/infected male was 1.6. Universal NAAT screening was the most cost-effective strategy, preventing 37 more cases of pelvic inflammatory disease (PID) and 3 more cases of epididymitis than selective screening and saving an additional $24,000. The analysis was sensitive to NAAT cost, LE sensitivity, rate of PID development, PID sequelae cost, and number of female partners. Universal screening remained the most cost saving for prevalence as low as 2.8% or higher.Universal chlamydia screening of adolescent males on entry to detention was the most cost-effective strategy. Savings are primarily the result of the prevention of PID in recent and future partners of index males. Screening detained male youth using a urine-based NAAT provides a public health opportunity to significantly reduce chlamydia infections in youth at risk for sexually transmitted diseases.