Preemptive therapy for cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplant (HSCT) patients is effective in decreasing the incidence of CMV disease. Intravenous ganciclovir is a commonly used preemptive therapy, but as we have recently shown, oral valganciclovir (VGC) is a useful alternative. However, the optimal dose of VGC has not been determined. We prospectively evaluated the efficacy and toxicity of an initial low-dose of VGC (900 mg QD) as preemptive therapy in 20 patients with low-level CMV antigenemia following allogeneic HSCT. Patients were screened weekly for CMV pp65 antigenemia after engraftment. Preemptive therapy with VGC (900 mg QD) was initiated if more than two CMV antigen-positive cells per 50,000 leukocytes were detected. CMV antigen-positive cells disappeared from all 20 patients after 14-29 days (median 20 days) of VGC treatment. None of the patients developed CMV disease nor did they require more than the conventional VGC dose (900 mg BID). Neutropenia (<500/μL) developed in three patients who required granulocyte-colony-stimulating factor support, but there were no other significant side effects. These observations suggest that the initial dose of VGC in preemptive therapy for CMV can be safely decreased to 900 mg QD for patients with low-level CMV antigenemia.