Background: Wide-scale application of urine-based screening of asymptomatic men for chlamydial infection has not been thoroughly assessed. Goal: The goal was to compare clinical and economic consequences of three strategies: (1) no screening, (2) screening with ligase chain reaction (LCR) assay of urine, and (3) prescreening urine with a leukocyte esterase test (LE) and confirming positives with LCR. Study Design: We used a decision analytic model. Results: At a chlamydia prevalence of 5%, the no screening cost was $7.44 per man screened, resulting in 522 cases of pelvic inflammatory disease (PID) per 100,000 men. LE-LCR was most cost-effective, preventing 242 cases of PID over no screening at an additional cost of $29.14 per male screened. The LCR strategy prevented 104 more cases of PID than LE-LCR but cost $22.62 more per male screened. For this to be more efficient than LE-LCR, the LCR assay cost needed to decline to ≤$18. Conclusion: At a chlamydia prevalence of 5%, LE-LCR is the most efficient use of resources. If LCR cost decreases or chlamydia prevalence increases, the LCR strategy is favored.