The aim of this study was to understand the impact of chronic graft-versus-host disease (cGVHD) on the overall health status of hematopoietic cell transplantation (HCT) survivors. Subjects included 584 individuals who had undergone allogeneic HCT between 1976 and 1999, survived 2 or more years, and completed a 255-item health questionnaire. Global assessment of health status was facilitated by measurement of 6 health status domains: general health, mental health, functional impairment, activity limitation, pain, and anxiety/fear. Information regarding diagnosis of cGVHD was abstracted from medical records, and presence of active cGVHD in the preceding 12 months was self-reported. The incidence of cGVHD in participants was 54%, of whom 46% reported active cGVHD. In multivariable analyses, subjects with active cGVHD were more likely to report adverse general health, mental health, functional impairments, activity limitation, and pain than were those with no history of cGVHD. However, health status did not differ between those with resolved cGVHD and those who never had cGVHD. We conclude that active cGVHD has a significant impact on many aspects of the overall health status of HCT survivors and that, most importantly, those successfully treated for cGVHD do not appear to have long-term impairments. © 2006 by The American Society of Hematology.