Infectious complications following allogeneic hematopoietic cell transplantation (HCT) from unrelated donors (URD) result in significant morbidity. We hypothesized that recipients of a URD with an activating natural killer cell immunoglobulin-like receptor (KIR) (B/x) genotype would have decreased infectious complications because of enhanced natural killer (NK) cell function. We compared the infectious complications in 116 recipients of a graft from a donor with an A/A KIR (n = 44) genotype and a B/x KIR (n = 72) genotype. All recipients participated in the prospective National Marrow Donor Program infection project collecting infection data from conditioning until 6 months posttransplant. The cohort with a B/x donor had fewer initial bacterial infections by day 180 (A/A: 86%; 95% confidence interval [CI], 75-95; B/x: 68%; 95% CI, 57-78; P = .02). There was no difference in the incidence of viral or fungal infections. When accounting for multiple infections, fewer bacterial infections were seen in the B/x cohort (A/A: 3.55/patient; B/x: 2.63/patient; P = .09). During the study period, only 19 patients had no infections; of these, 15 had received cells from a B/x KIR donor. The role of donor KIR genotype on infection complications is intriguing and warrants further investigation.