To evaluate and compare the health-related quality of life (HRQOL) of patients with newly diagnosed CML in the first chronic phase (CML-CP1) receiving HLA-identical sibling donor (ISD) hematopoietic SCT (HSCT) or imatinib, a cross-sectional study that was part of a prospective cohort study at the Institute of Hematology, Peking University was performed. A total of 222 patients including 126 and 96 in the imatinib and ISD HSCT groups, respectively, were enrolled. HRQOL was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey. The ISD HSCT group functioned significantly better on the role-physical functioning and mental health subscales, as well as the mental component summary (MCS) than the imatinib group. HRQOL was generally comparable to groups in the young population. Multivariate analysis showed that white blood cell count ≥ 30 × 10(9)/L and plts count ≥ 450 × 10(9)/L were the major adverse factors affecting HRQOL in long-term survivors. Imatinib therapy was also an adverse factor affecting the MCS (odds ratio=1.7, P=0.032). Thus, long-term CML-CP1 survivors receiving ISD HSCT can attain desirable HRQOL comparable to or better than that of patients receiving imatinib.