It is unclear whether valganciclovir (VGCV) is effective compared with intravenous ganciclovir (GCV) for preemptive therapy of cytomegalovirus (CMV) infection in living donor liver transplantation (LDLT). A randomized trial was conducted to compare the efficacy of oral VGCV with intravenous GCV for preemptive treatment of CMV infection after LDLT. Patients who developed CMV infection within 6 months after LDLT at Tokyo University Hospital were randomly assigned to the VGCV or GCV group and received either oral VGCV 900 mg/day or intravenous GCV 5 mg/kg twice daily, respectively. The primary endpoint was the treatment success rate. Secondary endpoints were recurrence of CMV infection within 1 year after finishing the treatment, and safety and tolerability of the treatment. Twenty-two patients with CMV infection after LDLT fulfilled the inclusion criteria and were randomly assigned to the oral VGCV group (n = 11) or the intravenous GCV group (n = 11). Treatment success rates were 82% (9 of 11) and 91% (10 of 11) in the VGCV and GCV groups, respectively. One patient in the VGCV group developed recurrence, whereas no patients in the GCV group developed recurrence. All the patients completed the treatment protocol, and no patients in either group dropped out of the study. In conclusion, oral VGCV and intravenous GCV are safe, feasible options for preemptive treatment of CMV infection after LDLT.