To explore risk factors affecting HrQoL, we analyzed data from patients (n = 51) at least three yr beyond SCT and their parents (n = 41), who responded to the SCHQ, to a subjective symptom inventory and to a sense of coherence instrument, in parallel with a physician-rated scoring of late effects. Children with leukemia rated a lower HrQoL than children with non-malignant disease only in subscale RE, limitations in role socially because of the emotional difficulties (p < 0.05) but had more severe late effects (p < 0.05). Parents of children with leukemia rated their children's HrQoL overall lower in both the psychosocial area and physical area (p < 0.01) and the child's condition also had a greater impact on parents' emotional situation (p < 0.05), compared with parents of children with non-malignant diagnosis. The psychosocial HrQoL was more affected in recipients of an unrelated than of a sibling graft, according to both child (p < 0.01) and parent (p < 0.05). In the multiple regression analysis, however, late effects remained the only independent factor, contributing to low parental psychosocial (p < 0.05) and physical (p < 0.001) HrQoL ratings, while leukemia, unrelated donor and TBI did not. To conclude, parent-reported HrQoL was lower in SCT patients with leukemia, mainly due to a higher impact of late effects in this group.