Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay®. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. × 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.