OBJECTIVES: Combination therapy with an α-blocker and an antimuscarinic is recommended for men with moderate-to-severe LUTS/BPH if symptom relief is insufficient with monotherapy. We evaluated the cost-effectiveness of fixed-dose combination (FDC) solifenacin 6mg + oral controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS, 0.4mg) versus tolterodine (modified release, 4mg) + tamsulosin (0.4mg) given concomitantly, from the perspective of the UK NHS.  METHODS: A Markov model, with a time horizon of 1 year, was developed for men with LUTS/BPH who have moderate-to-severe storage symptoms (≥8 micturitions/day and ≥2 urgency episodes/day [Patient Perception of Intensity of Urgency Scale, PPIUS, grade 3 or 4]) and voiding symptoms treated with FDC solifenacin 6mg + TOCAS or tolterodine + tamsulosin. Treatment success was defined using the Total Urgency and Frequency Score (TUFS, the daily sum of all recorded PPIUS scores from micturition diaries). The phase 3 NEPTUNE study was used to estimate transition probabilities and utilities were derived from analysis of EQ-5D data. Other model input parameters included discontinuation rates, derived from a large UK database study (THIN). Univariate and probabilistic sensitivity analyses were performed. RESULTS: FDC solifenacin 6mg + TOCAS was associated with lower total annual costs (£520 vs £583) and increased quality adjusted life years (QALYs, 0.840 vs. 0.838), and was therefore dominant compared with tolterodine + tamsulosin. Time horizon, discontinuation/withdrawal rates, drug cost and utility values were the main drivers of cost-effectiveness. The probability that FDC solifenacin 6mg + TOCAS is cost-effective was 100% versus tolterodine + tamsulosin, at a willingness to pay threshold of £20,000/QALY gained. CONCLUSIONS: FDC solifenacin 6mg + TOCAS is dominant compared with tolterodine + tamsulosin for the treatment of men with LUTS/BPH who have moderate-to-severe storage symptoms and voiding symptoms. To our knowledge, this is the first cost-effectiveness analysis of a FDC in this patient population.