In this multicenter, randomized study, cytomegalovirus (CMV)-seropositive patients who received an allogeneic bone marrow transplant were provided high-dose intravenous acyclovir (500 mg/m(2) q8h) from the day of transplantation until engraftment. The patients were then randomly assigned to receive either oral valacyclovir, 2 g q.i.d. (n=83), or intravenous ganciclovir, 5 mg/kg q12h for 1 week, then 6 mg/kg once daily for 5 days per week (n=85), until day 100 after transplantation. CMV infection occurred in 12% of the patients who received valacyclovir and in 19% of the patients who received ganciclovir (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.391-2.778; P=.934). CMV disease developed in only 2 patients who received valacyclovir and in 1 patient who received ganciclovir (HR, 1.943; 95% CI, 0.176-21.44; P=.588). Oral valacyclovir can be an effective alternative to intravenous ganciclovir for prophylaxis of CMV disease after bone marrow transplantation.