A significant proportion of potential kidney transplant candidates continue to periodically require blood transfusions that carry a risk of allosensitization. Leukocyte reduction (leukoreduction) of blood products has been proved to reduce transfusion-associated allosensitization in patients with hematologic malignancies; however, the effect in potential kidney transplant candidates is unknown. A total of 112 kidney transplant candidates who received red blood cell transfusions while on the transplant waiting list were identified retrospectively. Sixty received a transfusion before leukoreduction (non-LR), and 52 received a transfusion after the local implementation of universal leukoreduction of blood products (LR). There was no difference in transfusion-associated allosensitization rates in patients who received a transfusion during the two eras (non-LR 27% [16 of 60] versus LR 33% [17/52]; NS). Likewise, no difference was observed in subgroups identified as being at high risk of allosensitization (previous pregnancy, transplant, or five or more previous transfusions) or at low risk (no previous allogeneic exposures) (high risk: non-LR 52% versus LR 55%; low risk: non-LR 10% versus LR 8%). Multivariate analysis revealed previous pregnancy to be the only significant risk factor associated with transfusion-associated allosensitization (relative risk, 8.2; 95% confidence interval, 2.4 to 24.0; P = 0.0001). Leukoreduction, in particular, was not associated with any protective effect. In summary, leukoreduction of red blood cell transfusions does not confer any protection against transfusion-associated allosensitization for potential kidney transplant candidates. Physicians who care for patients with ESRD must continue to practice careful transfusion avoidance while alternative strategies to minimize transfusion associated allosensitization are sought.