A retrospective cohort study was conducted to determine the incidence of major infectious complications after orthotopic liver transplantation and to compare outcomes in patients receiving either cyclosporine (CsA) or FK506 (tacrolimus) as primary immunosuppression. Of 133 transplants performed in 118 patients, 124 transplant episodes were evaluated. Cytomegalovirus (CMV) infection (INF) and disease (DIS), deep fungal infection (DFI), and intraabdominal bacterial infections (IAI) were catalogued. The overall incidences of major infectious outcomes were: CMV INF = 33%; CMV DIS = 19%; DFI = 15%; and IAI = 25%. Cox proportional hazard analysis identified donor seropositivity, OKT3 as secondary immunosuppression and initial intensive care unit (ICU) duration as risk factors for CMV INF and DIS in the overall population. Fungal colonization was the dominant risk factor associated with deep fungal infection. A choledochojejunostomy anastomosis, the number of cellular blood products transfused at the time of transplantation surgery, and prior CMV INF were independent risk factors for both fungal colonization and deep infection. The single risk factor identified for intraabdominal bacterial infections was the number of cellular blood products transfused at the time of surgery. In the Cox proportional hazards model the relative risk (RR) for each category of infection was lower in the FK506 group (CMV: RR = .87, 95% confidence interval [C.I.] = [.32-2.4]; DFI: .58 [.13-2.6]; IAI: .51 [.15-1.7]), but the effect was not statistically significant. Survival was similar in patients receiving FK506 or CsA. CMV INF and DFI were independent predictors of death for all patients. Risk factors identified for CMV INF and DIS support the findings of others. Higher intraoperative blood product requirements and complicated intraoperative or postoperative courses increase the risk for IAI or DFI. The development of effective strategies to prevent CMV and fungal infections in liver transplant recipients remains a priority for future endeavors.