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To perform a cost-benefit analysis of a Chlamydia trachomatis screening program based on first-void urine testing of asymptomatic women using a polymerase chain reaction (PCR) test.A decision tree was developed. Selected variables based on assumptions were subjected to sensitivity analyses to make the model accurate and defensible.Screening for chlamydial infections using the PCR test was shown to be cost-effective even in lowprevalence populations. Compared with a symptom-driven no-screening situation, a universal C trachomatis screening program using the PCR test would save money, in terms of direct cost, when the baseline prevalence of C trachomatis infection exceeds 3.9%.Cost analyses are still rare among trials that compare pharmacologic or procedural health care interventions. Socioeconomic studies linking secondary prevention of C trachomatis infection and infertility and adverse pregnancy outcome are needed to convince public health authorities of the need for and the benefit of such programs.