Background: Cytomegalovirus (CMV) has long been recognized as the most common opportunistic pathogen in transplant recipients. The use of post-detection antiviral treatment of CMV as a strategy to prevent disease in cardiac recipients is becoming the standard policy. Valganciclovir is an oral pro-drug of ganciclovir, with a 10-fold greater bioavailability than oral gancyclovir. Patients and Methods: We reported our first experience with 8 patients (3 female, 45.0 +/- 10.5 years old, non-CMV mismatched) who underwent cardiac transplantation and had positive results of CMV polymerase chain reaction (PCR) within first 6 weeks after transplantation without concomitant CMV disease. These patients received valganciclovir in dosage 450 to 900 mg daily depending on renal function for 3 weeks. Standard immunosuppressive regimen consisted of cyclosporin A, MMF and corticosteroids, and was not changed after detection of CMV infection. In,one patient we used sifolimus with respectively reduced dosage of cyclosporin A. Weekly measurements of CMV-PCR were performed to observe results of therapy. Results: After 1 week of valganciclovir therapy CMV-PCR plasma concentration in all patients decreased significantly (2,105 copies/ml vs 400 copies/ml; p < 0.0001). No relapse of CMV infection has been detected after completing of valganciclovir therapy with follow up duration of 9.0 +/- 0.92 months. The drug was generally well tolerated, and we did not observe any severe drug related adverse events. Conclusion: Oral valganciclovir as pre-emptive antiviral therapy administrated after detection of CMV infection seems to be an effective and safe treatment in cardiac transplant recipients. J Heart Lung Transplant.