Reports on the efficacy of intravenous immunoglobulin (IVIG) prophylaxis againstcytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplantation (HCT) have often sparked controversy. In addition, we are not aware of any study thathas examined whether prophylaxis with IVIG affects the incidence of CMV infection inpatients who are at high risk of infection; those who are elderly or have receivedHLA-mismatched HCT. In the present open-label, phase II study, we addressed thisquestion. A total of 106 patients were enrolled on the study. The cumulative incidences of CMVinfection 100 days after HCT were similar in the intervention and control groups (68 and 64%, P = .89; 89 and 87%, P = .79, respectively for older patients and those who received HLA-mismatched HCT). In those who receivedHLA-mismatched HCT, 1-year overall survival after HCT was 46% in the interventionand 40% in the control group (P = 0.31); for age >55 years, the corresponding valueswere 46 and 40% (P = 0.27). Our data show that prophylaxis with regular polyvalent IVIG did not affect theincidence of CMV infection or survival in older patients or those who receivedHLA-mismatched HCT.