The objective of this study was to evaluate the clinical outcome of the treatment of hematologic malignancies with alternate hemibody irradiation (AHBI) combined with high-dose chemotherapy. Seventeen patients with hematologic malignancies were treated with AHBI combined with high-dose chemotherapy. Following high-dose chemotherapy, upper hemibody irradiation (UHBI) and lower hemibody irradiation (LHBI) were given sequentially in a dose of 6 to 9 Gy. UHBI was given 14 days (range, 12-22 days) after high-dose chemotherapy, and LHBI was performed 23 days (range, 7-34 days) after UHBI. Meanwhile, we treated a control group of 14 patients with acute lymphoblastic leukemia (ALL) with autologous hematopoietic stem cell transplantation (AHSCT). Hematopoietic reconstitution was observed in all of the patients. The median follow-up period was 927 days (range, 428-1446 days). The 3-year probabilities of disease-free survival (DFS) were 52.38% +/- 13.47% for the patients in complete remission who underwent AHBI. No patient died of AHBI-related toxicity. The 3-year DFS rates for the 2 groups of patients with ALL were not significantly different (47.73% +/- 17.55% in the AHBI group and 53.88% +/- 14.08% in the AHSCT group; P > .05). AHBI combined with high-dose chemotherapy is a feasible approach for patients with hematologic malignancies and has the advantages of a desirable effectiveness, low costs, simple operation, and acceptable side effects.