We prospectively followed 70 CMV-seropositive solid organ transplant recipients to evaluate the efficacy and safety of valganciclovir (VGCV) as preemptive therapy based on antigenemia test to prevent cytomegalovirus (CMV) disease. From December 2003 to May 2004, 12 of 70 (17%) asymptomatic patients who showed an antigenemia value > or =25 positive cells per 2 x 10(5) polymorphonuclear (PMN) were treated with VGCV (900 mg twice a day adjusted to renal function) until resolution of CMV antigenemia, a minimum of 14 days. No patient developed CMV disease during follow-up. Only one who showed an asymptomatic relapse of the antigenemia test > or =25 positive cells was successfully treated with a repeated course of VGCV. Mean duration of VGCV therapy was 18 days (range, 14 to 28). Antigenemia was negative in 7 of 12 (58%) patients after 14 days and negative in all patients 4 weeks after the administration of VGCV. No significant side effects were associated with the use of VGCV therapy. Preemptive VGCV therapy is safe and effective in the prevention of CMV disease in seropositive solid organ transplant recipients.