Reported results of high-dose therapy (HDT) reflect the combined effect of initial therapy and HDT. The incremental contribution of HDT is often difficult to analyze with varying degrees of response pre-HDT. Here we analyze results of HDT in patients with measurable disease at transplant, defined as a serum or 24 h urine M protein of >1.0 g per 100 ml and >200 mg per day, respectively. Paraprotein responses were calculated using measurements prior to HDT and the lowest subsequent measurement. A total of 431 patients were studied; 264 (61.3%) transplanted within 1-year of diagnosis. An additional reduction in paraprotein by 50% following HDT was seen in 86% patients; with 129 patients (30%) obtaining a 90% reduction. Patients with at least a 90% reduction had longer time to progression with no overall survival advantage and this was independent of other prognostic factors for decreased risk of progression. This study provides an estimate of the degree of tumor reduction provided by HDT, in addition to that provided by the initial therapy. In this group of patients with measurable disease after initial therapy, HDT therapy leads to complete responses in nearly a quarter of the patients and a 90% reduction in another 7%, an outcome associated with better progression-free survival.