OBJECTIVES: To estimate the incremental cost-effectiveness of bortezomib plus melphalan and prednisone (VMP) compared with melphalan, prednisone and thalidomide (MPT) and melphalan plus prednisone (MP) for the treatment of first-line multiple myeloma in Sweden. METHODS: We constructed a decision-theoretic model, using Microsoft® Excel 2007 to compare the VMP, MP and MPT regimens. Treatment effects of VMP and MP on progression-free survival and overall survival (OS) were obtained from the VISTA trial. Effects of MPT vs. MP were obtained from published reports of five randomized trials. Costs include drug and administration costs, adverse events, treatment of relapses, and end-of-life costs. Utility estimates are derived from the literature. A mixed treatment comparison meta-analysis indirectly compares VMP vs. MPT. The analytic framework is based on ‘partitioned survival analysis’ that allows survival data to be decomposed into three states: 1) alive before disease progression; 2) alive after progression; and 3) dead. The model estimates mean OS, quality-adjusted life-years (QALYs), costs and cost per QALY over a 30-year time horizon, and performs both 1-way and probabilistic sensitivity analyses. RESULTS: VMP’s mean OS is 61 months compared to 42.7 and 50.2 months for MP and MPT, respectively. Mean lifetime direct medical costs per patient are approximately SEK 1,193,000, 604,000 and 920,000 for VMP, MP and MPT, respectively. Mean incremental cost per QALY of VMP compared to MP is SEK 676,415; 90 percent C.I. (335,578, 710,135) and SEK 576,823; 90 percent C.I. (0, 1,444,278) compared to MPT. The two most influential variables in our model are 1) VMP to MP hazard ratio; and 2) utility after progression. CONCLUSIONS: VMP and MPT are projected to prolong survival relative to MP. Having ICERs less than SEK 700,000, we believe that from a Swedish perspective, VMP is cost-effective compared to both MP and MPT.