Background. Two serologic syphilis screening algorithms recommended by the US Centers for Disease Control and Prevention (US CDC) and the European Centre for Disease Prevention and Control (ECDC), respectively, are commonly used for syphilis screening; however, which one is optimal remains to be determined. Methods. We conducted a prospective study of 119 891 subjects to analyze the consistency of the US CDC- and ECDC-recommended algorithms. The US CDC-recommended algorithm begins with a treponemal immunoassay, followed by a rapid plasma reagin (RPR) test. RPR-nonreactive samples are confirmed by the Treponema pallidum particle agglutination assay (TPPA). The ECDC-recommended algorithm begins with a treponemal immunoassay, followed by a confirmatory treponemal test. If the confirmatory test is reactive, a quantitative nontreponemal assay is used to assess the disease activity and treatment response. In the present study, a total of 119 891 serum samples from a large hospital (sixth largest in China) were included, and each sample was screened with a chemiluminescent immunoassay (CIA). CIA-reactive samples were then simultaneously tested with RPR and TPPA. The consistency of these 2 algorithms was determined by calculating the percentage of agreement and. coefficient. Results. The overall percentage of agreement and kappa value between these 2 algorithms were 99.996% and 0.999, respectively. The positivity rate for syphilis as determined by the US CDC- and ECDC-recommended algorithms was 1.43% and 1.42%, respectively. Conclusions. Our results suggest that the US CDC-recommended algorithm and the ECDC-recommended algorithm have comparable performances for syphilis screening in low-prevalence populations.