We retrospectively compared survival time, quality of life, and the therapy costs in 37 patients suffering from newly diagnosed multiple myeloma (MM), divided into 3 groups. Twelve patients with grade III MM, according to the classification of Durie-Salmon, all with widespread lytic lesions (group I), underwent a two-phase intensive therapy. They first received high-dose melphalan (HDM), both as tumor-reducing and blood cell (BC)-mobilizing chemotherapy, subsequently followed by BC transplantation. Group II comprising 10 patients, also with grade III MM and with characteristics similar to those of group I, were treated with conventional polychemotherapy. Finally, group III enrolled 15 patients with lower grade disease (grade II) who were also treated with conventional chemotherapy. The median overall survival time and the quality of life index were significantly lower in group II than in group I (P = 0.0013 and < 0.001 respectively). Although the overall survival time of group III (43 months) was similar to that of group I, its quality of life index was also significantly lower (P < 0.05). However, the total therapy costs of group I were globally higher than those of the 2 other groups, but when absolute cost-effectiveness as well as qualitative cost-effectiveness (corrected for quality of life) were analyzed, the costs per week of life gained of group I compared extremely favorably with those of group II and, to a lower degree, of group III. Intensive therapy therefore seems capable of substantially improving the survival time for high-risk MM patients with satisfactory quality of life and at a reasonable cost.