Objective In three pilot regions of the Netherlands, all 16–29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data.

Methods A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16–29 years annually; 16–24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower (‘national network’) and higher (‘urban network’) baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed.

Results In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50 000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232 000 in the national and €145 000 in the urban sexual network. Results were robust in sensitivity analyses.

Conclusions It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50 000) screening may be more cost-effective than no screening.