Objectives: HLA antibodies in the serum of patients on the kidney transplantation Waiting list can cause impaired function, shortened graft survival time, and series of other adverse effects. Therefore, screening of serum for the presence of HLA antibodies and determining their specificity is an extremely important part of the immunogenetic testing of potential recipients. At the Tissue Typing Laboratory Rijeka, serum screening is performed by the CDC (Complement-Dependent Cytotoxicity) method and, since 2012, by a method based on Luminex technology whose features, advantages and disadvantages are presented in this research. Patients and Methods: The retrospective study included 1 524 serum samples of potential kidney recipients tested with two methods (CDC and Luminex) at the Tissue Typing Laboratory at the Clinical Hospital Center Rijeka from 2012 until the end of 2018. Sera were divided into groups among who the results of the Luminex test were compared. Results: The presence of HLA antibodies was detected in a significantly higher number of sera by the Luminex technique in comparison to the CDC method. Higher Mean-Fluorescence Intensity (MFI) had CDC-detected antibodies compared to antibodies determined by the Luminex technique only (cut-off MFI for HLA class I> 9 204). The highest MFI values had antibodies on HLA-B locus and the lowest against HLA-C locus. Conclusion: The Luminex is significantly more sensitive technique compared to the CDC method. However, the HLA antibodies detected by the CDC method present an absolute contraindication for transplantation, whereas the clinical role of antibodies determined by Luminex technology only is ambiguous. Because of that, in determination of unacceptable HLA antigen mismatches it is best to use the results of both methods, taking into account the advantages and limitations of each individually.