CMV infection is the commonest viral infection after solid organ transplant transplantation leading to significant morbidity and mortality. Ganciclovir has been proven to be effective to prevent and treat CMV infection. Recently Valganciclovir (Valgan; Gannciclovir Hydrochloride) has been found to have significantly better absorption compared to gannciclovir (450 mg valgan absorption is equivalent to 3 gm oral ganciclovir absorption and 900 mg valgan equivalent to 5mg/kg intravenous ganciclovir) and has been suggested as prophylaxis for prevention of CMV infection after solid organ transplantation. Aim of the present study is to examine the efficacy of valgan prophylaxis after primary liver transplantation. Between July 2001 to May 2003, 203 consecutive post-liver transplant recipients (129 males, 74 females, mean age 53+11 years) received valgan prophylaxis (900 mg/day to 450 mg/every other day depending on the renal function.) for 3-6 months. All patients were followed for a minimum of 6 months. PCR positive CMV in peripheral blood diagnosed symptomatic CMV. [Routine periodic surveillance of blood PCR was not performed]. The rate of CMV infection was stratified according to donor and recipient status of CMV antibodies. GroupI= Donor +/Recipient +, Group II= Donor -/Recipient +, GroupIII= Donor +/Recipient, and GroupIV= Donor -/Recipient. During the follow up period 29(14.3%) patients developed CMV (Positive by PCR in peripheral blood), of these 5 patients had invasive CMV on liver biopsies. The incidence was highest in Group III -14/54(25.9%) and lowest in Group IV- 0/35. In Group I and II, it was 16.4%(12/73) and 7.3% (3/41) respectively. Mean time to symptomatic CMV infection was 169 +117 (median174) days post transplantation. The rate of CMV for either donor or recipient positive status (Group I, Group II, and Group III) was 17.3% with an invasive CMV hepatitis rate of 3%. Overall rate of symptomatic CMV was 17.3% in either donor or recipients positive for CMV antibody despite high dose prophylaxis of valcyte, suggesting ineffectiveness of valcyte oral prophylaxis for prevention of symptomatic CMV in liver transplant recipients.