To estimate the cost-effectiveness of a systematic one-off Chlamydia trachomatis (CT) screening program including partner treatment for Dutch young adults. Data on infection prevalence, participation rates, and sexual behavior were obtained from a large pilot study conducted in The Netherlands. Opposite to almost all previous economic evaluations of CT screening, we developed a dynamic Susceptible-Infected-Susceptible (SIS) model to estimate the impact of the screening program on the incidence and prevalence of CT in the population. SIS models are widely used in epidemiology of infectious diseases, for modeling the transmission dynamics over time. Subsequently, a predictive decision model was used to calculate the complications averted by the screening program. Cost-effectiveness was expressed as the net costs per major outcome averted (MOA) and was estimated in the baseline analysis and in sensitivity analysis. The overall prevalence decreased from 1.79% to 1.05% as a result of the screening program directed at both men and women. The program costs were mainly offset by the averted costs, although not fully. Resulting net costs per MOA were 373 in the baseline analysis. Sensitivity analysis showed that partner treatment and sending a reminder are important aspects improving cost-effectiveness. Additionally, restricting the screening to women only was estimated to save costs. Our cost-effectiveness analysis shows that the Dutch society has net to pay for the prevention of CT-complications through screening young men and women. One could argue although that 373 per MOA presents a reasonable cost. A screening program consisting of screening women only should always be adopted from a pharmacoeconomic point of view. Our dynamic approach appreciates better the specific characteristics of an infectious disease, such as CT.