Abstract Introduction Complete prevention of cytomegalovirus (CMV) disease continues to be an unresolved problem in renal transplantation. Materials and Methods From January 2005 to May 2006, we implemented a protocol for early detection and preemptive treatment of CMV infection as detected by antigenemia or polymerase chain reaction determined every 2 weeks during the first 3 months posttransplant and monthly thereafter. Prophylaxis was given to all CMV-negative patients who received CMV-positive kidneys and to those who received polyclonal or monoclonal antibody induction therapy. Results Among 100 transplants, 15 subjects received prophylaxis due to poly- or monoclonal antibody induction and/or negative recipient serology using a mean valgancyclovir dose of 485 ± 276 mg/d for an average duration of 129 days. After completion of the prophylaxis four patients (26.6%) required preemptive therapy for asymptomatic virus reactivation; the mean dose of drug in these patients had been 450 ± 275.56 mg, with a treatment time that was significantly shorter than those not suffering reactivation (91.75 vs 143.45 days). In addition, preemptive therapy was given for virus reactivation in seven patients, for illness with mild viral syndrome in two, with moderate illness and positive pretransplantation serology in one. The average treatment time was 79 days and the mean dose was 375 mg. Conclusion In those not at risk, CMV infections occurred among 11.7% of patients in our early detection program. Prophylaxis for at-risk patients should continue for more than 3 months to prevent reactivation.