Background: Patients awaiting kidney transplantation are regularly screened for HLA-antibodies, but there is scarce data about the optimal interval. Methods: Results from Complement-dependent cytotoxicity testing (CDC) for waitlisted patients were reviewed for increases in panel reactive antibodies (PRA) by at least 10%-points. Clinical records were screened for historic immunizing events and possible trigger factors preceding the PRA-increase. Additionally, non-pretransplanted men tested negative for HLA antibodies by solid-phase assays (SPA) out of their first two samples on the waiting list (“non-immunized men”) were evaluated for detection of HLA antibodies by SPA during their further stay on the waiting list. Results: 15,360 samples from 1928 patients tested by CDC were analyzed for changes in PRA. PRA-increases occurred most frequently in patients waitlisted recently for retransplantation (annual incidence 6%). Removal of previous transplants, severe infections and/or reduced immunosuppression triggered 65% of PRA-increases during the first year after waitlisting. Transfusions accounted for 55% of PRA-increases in later years. Leucocyte-reduced red blood cell units not only boosted historic antibodies, but even induced primary immunization. In the second part of the study, 6780 samples tested by SPA from 703 non-immunized men were evaluated for development of HLA-antibodies. Only 9 men (1.3%) turned HLA antibody-positive (annual incidence 0.4%). Conclusion: A uniform screening interval does not fit all: Frequencies should be highest in patients newly waitlisted for re-transplant and lowest in non-immunized men. Transfused patients should be monitored closely for development of HLA-antibodies even if leukoreduced products are used.