BackgroundMost Chlamydia trachomatis (CT) infections are asymptomatic. The infection can persist and lead to severe sequelae. Therefore, screening for CT can primarily prevent serious sequelae.AimTo systematically evaluate CT screening from the perspective of health economics, summarize previous findings from different target populations, and make practical recommendations for developing local CT screening strategies.MethodsPubMed, Web of Science, Embase, Cochran Library, and National Health Service Economic Evaluation Database (Ovid) were searched from January 1, 2000, to March 4, 2023. Studies reporting the cost-effectiveness, cost-benefit, or cost-utility of CT screening were eligible to be included. A narrative synthesis was used to analyze and report the results following the PRISMA guidelines. The Consensus on Health Economic Criteria (CHEC) list was used to assess the methodological quality of included studies.ResultsOur review finally comprised 39 studies addressing four populations: general sexually active people (n = 25), pregnant women (n = 4), women attending STD and abortion clinics (n = 4), and other high-risk individuals (n = 6). The total number of participants was ~7,991,198. The majority of studies assessed the cost-effectiveness or cost-utility of the screening method. The results showed that the following screening strategies may be cost-effective or cost-saving under certain conditions: performing CT screening in young people aged 15–24 in the general population, military recruits, and high school students; incorporating CT screening into routine antenatal care for pregnant women aged 15–30; opportunistic CT screening for women attending STD and abortion clinics; home-obtained sampling for CT screening using urine specimens or vaginal swab; performing CT screening for 14–30-year-old people who enter correctional institutions (i.e., jail, detention) as soon as possible; providing CT screening for female sex workers (FSWs) based on local incidence and prevalence; adding routine CT screening to HIV treatment using rectal samples from men who have sex with men (MSM).ConclusionWe found that CT screening in general sexually active people aged 15–24, military recruits, high school students, pregnant women aged 15–30, women attending STD and abortion clinics, people entering jail, detention, FSWs, and MSM has health economic value. Due to the different prevalence of CT, diversities of economic conditions, and varying screening costs among different populations and different countries, regions, or settings, no uniform and standard screening strategies are currently available. Therefore, each country should consider its local condition and the results of health economic evaluations of CT screening programs in that country to develop appropriate CT screening strategies.