OBJECTIVES:  MM is the second most common haematological malignancy. With the recent introduction of new agents, survival has greatly improved. This study aimed to assess the cost-effectiveness of bortezomib (BOR) vs. dexamethasone (DEX) as second-line treatment of RRMM. Lenalidomide in combination with dexamethasone (LEN+DEX) was also considered in a secondary analysis. METHODS:  An area under the curve decision-analytic model was developed, containing three health states: “pre-progression”, “post-progression” and “dead”. Survival analyses of the APEX trial (BOR vs. DEX) were used to estimate the transition probabilities by line of treatment. As 71% of patients randomised to DEX crossed over to BOR, the hazard ratios (HR) were adjusted for crossovers (progression-free survival [PFS]: 0.56; overall survival [OS]: 0.59). HRs for LEN+DEX vs. DEX (PFS: 0.35; OS: 0.71) were retrieved from the MM-09/10 trials (not adjusted for 47.6% cross-over or line of treatment). Treatment schedule, compliance rate and adverse events (AEs) rates were retrieved from the above clinical trials, while utility weights were retrieved from the published literature. The model runs over patients’ lifetime, and discount rate of 3.5% was applied to costs and QALYs and assumptions around level of vial sharing for bortezomib were investigated. RESULTS:  BOR was associated with an incremental effectiveness of 1.56 life years gained (LYG) and 0.86 QALYs per patient compared to DEX, while LEN+DEX was found to be less effective (-0.64 LYG, -0.28 QALYs) than BOR. Scenario analyses showed BOR is cost-effective in most cases when compared to DEX, while LEN+DEX was dominated by BOR. The results were sensitive to treatment effect on survival. CONCLUSIONS:  The model suggests that BOR is a cost-effective option for treating RRMM in the UK.