Background: Rapid, point-of-care tests that accurately identify syphilis are gaining popularity and offer several advantages over classic tests. Methods: The SD Bioline Syphilis 3.0 and the Chembio DPP Syphilis Screen and Confirm Assay (CB) were assessed using 1283 samples that had been characterized by reference tests. The challenge samples included 5 commercial panels (seroconversion, mixed-titer), archived samples, fresh samples, and a dilution series. Both tests detect specific anti-treponemal antibodies, and the CB additionally detects antibodies to a non-treponemal (NT) component. The evaluation was used to determine performance indices and compare with those cited by the manufacturers. Results: When assessing reactivity to treponemal, the sensitivities for the 2 tests were 98.3% and 93.2%, with specificities of 100% and 99.4%, respectively. For both tests, precision, whole blood testing, and high-temperature testing produced perfect results, and there were no invalid results. Comparisons of 2 different lots of each test indicated excellent concordance (100% and 99.5%), and reproducibility was 100% and 98.0%, respectively. For the CB, the sensitivity for the NT component was between 65.3% and 80.9%, but increased to 98.5% with samples having a rapid plasma regain (RPR) titer of ≥8. The specificity for NT was found to be 100%, and the reading of results visually and when using a battery-operated reader indicated a concordance for all challenges of 95%-100%. Conclusions: Both rapid tests produced impressive results for the detection of antibodies to treponemal for all challenges and exceeded, met, or closely approached the performance characteristics as cited by the manufacturers. IMPACT STATEMENT The use of these rapid tests can assist patients in a variety of care venues, including in resource-limited countries, in physicians' offices so that positive patients are immediately connected to care, for pregnant women to improve infant morbidity, for transfusions to protect recipients, and for the timely treatment of syphilis. The information provided will inform potential users of the performance characteristics of the two tests being considered for adoption and provides a comparison with what the manufacturers state. The results contribute to the field by providing a comparative analysis of two tests that are used in many countries.