Infection remains a common source of morbidity and mortality after solid organ transplantation. The purpose of this study was to characterize the continuously changing patterns of post-transplantation infections, analyze early post-transplantation infections, and evaluate characteristics associated with mortality. A secondary analysis was performed on prospectively collected data for all episodes of infection occurring between 10 December 1996 and 28 October 1998 on the surgery services at a university medical center. Post-transplantation infections were compared with those in non-transplantation patients randomly matched by severity of illness. Further analysis was performed on post-transplantation infections occurring during the admission of transplantation compared with those in subsequent admissions. To evaluate factors associated with mortality, episodes occurring in survivors and non-survivors were compared. The results demonstrated that infections in transplantation recipients (n = 303) were associated with a younger age and had significantly lower white blood cell counts (WBC) compared with non-transplantation patients. There was no difference in mortality (15.5 vs. 16.5%, p = 0.74). Post-transplantation infectious complications during the initial hospitalization (n = 105) occurred at 38+/-6 compared with 695+/-66 d (p<0.0001) after transplantation and were associated with a longer length of stay (LOS) and increased mortality (30.5 vs. 7.6%, p<0.0001) compared with those occurring in subsequent admissions (n = 198). Although multiple characteristics of post-transplantation infections were associated with mortality, only the Acute Physiology and Chronic Health Evaluation (APACHE) II score was an independent predictor of mortality. Post-transplantation infections remain a significant source of morbidity and mortality. The leukocyte response to infection was suppressed in the transplantation population. Post-transplantation infections which occur during the admission for transplantation have a markedly increased mortality.