Abstract Background: In Turkey, prior to transfusion and apheresis, it is mandatory to screen blood for HBsAg, anti-HCV, anti-HIV 1/2, and syphilis. In recent years, efforts have been made to create effective diagnostic algorithms for screening, and as a screening strategy, many countries have switched from traditional algorithms to reverse algorithms. This study was carried out to evaluate the results we obtained after changing to chemiluminescence immunoassay (CLIA) based reverse algorithm, which is more sensitive and specific than the traditional algorithm and VDRL test we currently use for syphilis screening. Methods: The screening algorithm was initiated with the treponemal CLIA method. The reactive samples were tested using a nontreponemal test VDRL and a second treponemal test TPHA. In the descriptive analyses, the averages, numbers, and percentage distributions were calculated. The group comparisons were undertaken with the chi-square test, accepting p < 0.05 as statistically significant. Results: Of the 5,053 samples that were tested with CLIA syphilis TPA assay 5,043 were negative (99.802%) and 10 were positive reactive (0.198%), and the difference between the two was statistically significant (p < 0.001). Ten samples that were recurrently reactive were analyzed by VDRL and TPHA tests simultaneously. VDRL was negative in all 10 samples, whereas TPHA was negative in one sample, but positive in nine samples at a titer of ≥1/160. Conclusion: Based on the results of this study, we decided to use the CLIA method and reverse algorithm instead of using the traditional algorithm and VDRL as the initial screening method.