Cytomegalovirus (CMV) infection imposes a significant economic burden on susceptible patients after renal transplantation. Our study was conducted to determine the prediction, probability, consequences, and treatment costs of CMV infection under Canadian consensus guidelines in 270 sequential transplant patients. Transplant patients from donors positive (D(+)) for CMV into recipients negative (R(-)) for CMV received antiviral prophylaxis for 14 weeks and all but donor negative (D(-))/R(-) patients were monitored weekly for the CMVpp65 marker expression. Marker-positive patients and patients with CMV infection or disease received antiviral treatment. Within the first 6 months, 27% of the 270 patients tested had incidences of asymptomatic CMV infection, while 9% had CMV syndrome or disease. Only 1% of patients had infection after 6 months. The CMVpp65 marker levels were significantly greater in patients with syndrome or disease; but post-test probabilities and predictive value of the marker assay were low. Mean direct costs for care were $2256 and ranged from $927 for D(-)/R(-) patients to $7069 in the D(+)/R(-) patients. Extension of antiviral prophylaxis to D(+) or D(+)/R(+) patients significantly increased the estimated mean costs for an absolute reduction to 4% in CMV syndrome or disease. Our studies show that current guidelines for treatment enable effective control of CMV infection; however, alternative strategies have different economic impact.