Long-term results of high-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as the first-line treatment for patients with myeloma are still poorly reported. To gain further insight in the long-term benefits of first-line HDT-ASCT compared with conventional therapy in myeloma, we performed a meta-analysis of individual patient data. We selected randomized trials evaluating HDT-ASCT in patients with previously untreated myeloma from 1990 to 1998, all with a median follow-up of 5 years or more. Individual data of the 3 selected trials were obtained from the study authors. Outcomes were survival, treatment-related mortality, and time without symptoms of disease or toxicity of treatment (TWiST). Five hundred seventy-five patients were analyzed, including 435 deaths (104 months of median follow-up). Compared with conventional therapy and adjusting for prognostic covariates, HDT-ASCT did not significantly prolong long-term survival (stratified hazard ratio, 0.887; 95% confidence interval, 0.735-1.072). This was not modified by accounting for heterogeneity in baseline risks, in treatment of relapse, or in outcomes across trials. There was no evidence of interaction between treatment effect on survival and presentation features. In contrast, a mean gain of 14.5 months (95% confidence interval, 9.9-19.1 mo) in TWiST was observed in the HDT-ASCT group compared with conventional therapy. In conclusion, we showed only a trend toward a long-term survival benefit of HDT-ASCT over conventional therapy for first-line treatment of myeloma. However, HDT-ASCT clearly delayed time to relapse, with a resulting 14.5 months benefit in mean TWiST.