We prospectively evaluated the incidence of human herpesvirus 6 (HHV-6) DNAemia after allogeneic hematopoietic stem cell transplantation (HSCT) using quantitative plasma real-time polymerase chain reaction. Of 46 recipients of bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT) from related (n = 11) or unrelated donors (n = 22), and cord blood transplantation (CBT) from unrelated donors (n = 13), 22 (47.8%) developed HHV-6 DNAemia. HHV-6 DNA levels ranged from 200 to 200,000 copies/mL of plasma, and HHV-6 DNAemia was observed significantly more frequently after CBT than after BMT/PBSCT (92.3% vs 30.3%; P < .001). Multivariate analyses identified CBT (vs BMT/PBSCT), HLA mismatches between recipient and donor, and low anti-HHV-6 IgG titer before transplantation as the only risk factors for developing HHV-6 DNAemia. Three patients developed central nervous system (CNS) disorders with detectable HHV-6 DNA in the cerebrospinal fluid; all of these patients simultaneously developed HHV-6 DNAemia. These results suggest that HHV-6 DNAemia is frequently observed after allogeneic HSCT, especially in patients with the aforementioned risk factors. Thus, together with the assessment of risk factors, monitoring of HHV-6 DNAemia could be a useful asset in diagnosing HHV-6-associated CNS disorders.