OBJECTIVES: To explore whether existence of long-lasting partial immunity against reinfection with Chlamydia trachomatis is necessary to explain C. trachomatis prevalence patterns by age and sexual risk, and to provide a plausible estimate for the effect size, defined here as a reduction in susceptibility to reinfection. METHODS: A population-based mathematical model was constructed to describe C. trachomatis natural history and transmission dynamics by age and sexual risk. The model was parameterised using natural history, and epidemiological and sexual behaviour data, and applied for UK and US data. Sensitivity analyses were conducted to assess the robustness of predictions to variations in model structure and to examine the impact of alternative assumptions for the mechanism underlying partial immunity. RESULTS: Partial immunity against reinfection was found necessary to explain observed C. trachomatis prevalence patterns by age and sexual risk. The reduction in susceptibility to reinfection was estimated at 93% using UK data (95% uncertainty interval (UI)=88%-97%) and at 67% using US data (95% UI=24%-88%). The model-structure sensitivity analyses affirmed model predictions. The immunity-mechanism sensitivity analyses suggested a mechanism of susceptibility reduction against reinfection or a mechanism of infectious-period duration reduction upon reinfection. CONCLUSIONS: A strong long-lasting partial immunity against C. trachomatis reinfection should be present to explain observed prevalence patterns. The mechanism of immunity could be either a reduction in susceptibility to reinfection or a reduction in duration of infection on reinfection. C. trachomatis infection appears to naturally elicit a strong long-lasting immune response, supporting the concept of vaccine development.