OBJECTIVES: Treatment guidelines and recommendations endorse inhaled therapy with three molecules for eligible patients with COPD. Previously, triple therapy was only available through two separate inhalers. Treatment compliance and patient acceptability may improve with SITT, thereby, contributing to successful disease management. We assessed the cost-effectiveness of the new SITT composed of fluticasone furoate 100μg, umeclidinium 62.5μg, and vilanterol 25μg, (FF/UMEC/VI) versus commonly prescribed MITTs (tiotropium 18μg [TIO] + fluticasone propionate/ salmeterol [FP/SAL] 250/50μg [“MITT-250”] and TIO + FP/SAL 500/50μg, [“MITT-500”]) from a Canadian public payer perspective. METHODS: A validated linked risk equation model (Briggs, 2017 Med Decis Making 37:4), which predicts COPD disease progression, healthcare costs and health outcomes, was populated with baseline characteristics from RCTs conducted in patients eligible for triple therapy. Efficacy estimates were derived from a network meta-analysis (NMA). Canadian healthcare resource unit and drug costs were applied, with future costs and health outcomes discounted at 1.5% annually. A probabilistic analysis with a lifetime horizon modelled exacerbation rates, costs (2017 CAD), quality-adjusted life years (QALYs) gained and incremental cost effectiveness ratio (ICER) per QALY. A cost-utility analysis was required for Canadian health technology assessment. RESULTS: Compared with BUD/FOR, FF/UMEC/VI treatment resulted in fewer moderate and severe exacerbations (2.608 and 0.515 vs 2.126 and 0.306) and a mean (95% CI) incremental cost and health benefit of €325 (-€679, €1,338) and 0.02 (0.08, 0.13) QALYs, resulting in an ICER of €3,047 per QALY gained. The ICER was most sensitive to size of exacerbation treatment effect, duration of treatment effect, varying value (±20%) of resource use/event cost inputs, and time horizon. In the PSA, in 95% of 1000 simulations, the ICER fell between dominant and €12,768 for FF/UMEC/VI versus BUD/FOR, confirming robustness of the results. The probability of FF/UMEC/VI being cost-effective against BUD/FOR was 100% above a willingness-to-pay threshold of €14,000 per QALY gained. CONCLUSIONS: FF/UMEC/VI was deemed a cost-saving and similarly efficacious therapy relative to commonly used MITTs for the treatment of moderate/severe COPD in Canada.