ObjectiveTo identify the advantages and disadvantages of the rapid plasma reagin test (RPR), chemiluminescence immunoassay (CLIA) and Treponema pallidum particle agglutination test (TPPA) for detecting syphilis. MethodsA total of 1,808 serum specimens were detected by RPR and CLIA; the negative specimens as detected by CLIA and by RPR were redetected by TPPA.ResultsThere were 170 syphilis patients among the 1,808 patients.The sensitivity and positive predictive value of RPR were both significantly lower than those of CLIA and TPPA (P<0.05). The specificities were not significantly different between CLIA and RPR(P>0.05). However, the negative predictive value of RPR was significantly lower than that of CLIA (P<0.05). The sensitivities were not significantly different between CLIA and TPPA(P>0.05); however, the positive predictive value of CLIA was significantly lower than that of TPPA (P<0.05). Biologically false positive results could be found for all the 3 methods and false negative results could be found for RPR and TPPA (P<0.05). ConclusionCLIA and TPPA are superior to RPR in diagnosing syphilis. The procedure of diagnosing syphilis may need to be adjusted, and syphilis should be diagnosed by combining the medical history, symptom and lab results.