Chronic obstructive pulmonary disease (COPD) is associated with a substantial economic burden in the UK. Although previous analyses have compared the cost-effectiveness of single-inhaler triple therapy (SITT) versus dual therapy or multiple-inhaler triple therapy, there are no studies investigating the cost-effectiveness of individual SITTs versus other SITTs. This study assessed the cost-effectiveness of SITT with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus other SITTs for the treatment of COPD from a UK National Health Service perspective.The validated GALAXY-COPD model was populated with patient baseline characteristics from the IMPACT study and treatment effect data from a network meta-analysis, which compared FF/UMEC/VI with budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FOR; both 320 µg and 160 µg dosing; BUD320 and BUD160, respectively) and beclometasone dipropionate/formoterol fumarate/glycopyrrolate (BDP/FOR/GLY). UK healthcare resource unit and drug costs (Great British Pound, 2022) were applied, with costs and outcomes (except life years [LYs]) discounted at 3.5% annually. The base case was probabilistic (5000 iterations) with a lifetime horizon.FF/UMEC/VI provided an additional 0.620 (95% range: 0.255, 1.025) LYs and 0.283 (0.080, 0.501) quality-adjusted LYs (QALYs) with a cost saving of £1620 (£158, £3243) versus BUD320/GLY/FOR, an additional 0.627 (0.261, 1.053) LYs and 0.309 (0.097, 0.533) QALYs at a cost saving of £1721 (£261, £3345) versus BUD160/GLY/FOR, and an additional 0.328 (0.063, 0.654) LYs and 0.230 (0.035, 0.437) QALYs at a cost saving of £1221 (-£541, £2796) versus BDP/FOR/GLY. FF/UMEC/VI was less costly and showed higher QALYs in 98.2%, 98.9%, and 93.6% of simulations versus BUD360/GLY/FOR, BUD160/GLY/FOR, and BDP/FOR/GLY, respectively. At a willingness-to-pay threshold of £20,000 per QALY, the probability of FF/UMEC/VI being cost-effective was 99.9%, 100%, and 99.3% versus BUD320/GLY/FOR, BUD160/GLY/FOR, and BDP/FOR/GLY, respectively.Based on this analysis, FF/UMEC/VI is a dominant (improved outcomes with cost savings) treatment option compared with other SITTs for the treatment of patients with COPD in the UK.