OBJECTIVE: To determine how often cardiac allograft recipients develop infectious diseases and how the infections affect these patients. PATIENTS AND METHODS: We retrospectively studied 313 patients who underwent heart transplant at Mayo Clinic's site in Rochester, MN, from January 1, 1988, through June 30, 2006. RESULTS: In the early postoperative period (ie, period between heart transplant and discharge from the hospital), infectious diseases occurred in 70 (22%) of 313 patients but were not associated with 1-year mortality; the most commonly infected sites were the lungs (7%), bloodstream (6%), upper respiratory tract (5%), and urinary tract (4%). In the 18 years after transplant, the cumulative incidence of infectious diseases was 93%; the most common infectious complications were skin and soft tissue (63%), urinary tract (46%), cytomegalovirus (40%), lung (36%), upper respiratory tract (23%), and varicella zoster virus (15%) infections. After adjustment for baseline predictors, lung (hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.49-6.02; P<.001) and central nervous system (HR, 4.48; 95% CI, 1.75-11.46; P=.002) infections were predictive of mortality. Serum creatinine levels (HR, 1.74; 95% CI, 1.07-2.81; P=.02) and sirolimus use (HR, 2.72; 95% CI, 1.00-7.36; P=.05) were predictive of lung infection. Death occurred during the study period in 95 (30%) of 313 patients, with a cumulative incidence of 71% at 18 years. The cause of death was infection in 17 (18%) of 95 patients. CONCLUSION: Early postoperative infectious complications are frequent in cardiac allograft recipients but are not associated with 1-year mortality. Lung and central nervous system infections are predictors of mortality. © 2008 Mayo Foundation for Medical Education and Research.