The purpose of this study was to analyze the outcome of patients with multiple myeloma (MM) responding to initial chemotherapy who received intensification with high-dose therapy/autotransplantation (HDT) as compared to that of those who were continued on standard chemotherapy. From 1 January 1990 to 30 June 1998, 64 patients with MM who were younger than 65 years achieved a response to initial chemotherapy. Due to referral reasons, patients preference or inclusion in trials, 31 patients received HDT as early intensification while 33 were continued on standard chemotherapy. The presenting features were similar in both groups, except for the median age, which was lower in the HDT group (53 vs 58 years, P = 0.007). Complete response negative immunofixation - (CR) was achieved in 12 of 31 (39%) patients intensified with HDT and in two of 33 (6%) patients who were continued on conventional chemotherapy (P = 0.002). Event-free survival (EFS) was significantly longer in the HDT group (median, 43 vs 21 months; P = 0.007). Overall survival (OS) was not significantly different between groups (median, 62 vs 38 months; P = 0.21). However, patients in the HDT group who achieved CR had an EFS (median, 51 vs 31 months; P = 0.03) as well as an OS (median, not reached vs 50 months; P = 0.0006) significantly longer than those achieving a lower degree of response. In conclusion, this non-randomized study shows that early HDT increases CR rate and prolongs EFS. In addition, these results highlight CR as a crucial step for achieving long-lasting disease control and prolonged survival in patients with MM.