It has been established that high-dose chemotherapy (HDT) improves the therapeutic outcome of patients with multiple myeloma (MM) as compared with standard-dose therapy (SDT); however, little is known about the impact of HDT on different prognostic groups of MM patients. We therefore compared the survival times of 77 patients with previously untreated MM who were enrolled in HDT regimens with those of 64 similar patients <65 years old, who would be eligible for HDT but were treated by SDT. Overall, HDT was superior to SDT with respect to achievement of complete remissions (28% versus 2%; P <0.0001) and improvement of progression-free survival (PFS) (30.2 versus 21.2 months; P = 0.01) as well as overall survival (OS) (median 54.9 versus 49.4 months; P = 0.048). According to the chromosome 13q14 status as determined by fluorescence in situ hybridization and serum levels of beta(2)-microglobulin (beta(2)M), MM patients were separated into a standard-risk group (normal chromosome 13q14 and beta(2)M </=4 mg/l) and a high-risk group (deletion of chromosome 13q14 and/or beta(2)M >4 mg/l). Among patients of the high-risk group, both PFS (26.4 versus 10.7 months; P = 0.004) and OS times (40 versus 23 months; P = 0.05) were longer in patients receiving HDT compared with patients treated by SDT. In the standard-risk group, PFS and OS times were not significantly different between HDT patients and SDT patients. Results of this retrospective analysis suggest that the beneficial effects of HDT are greater in MM patients with high-risk features than in patients with absence of such poor prognostic indicators.