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Introduction Single-inhaler triple therapy (SITT) is known to be a cost-effective intervention for chronic obstructive pulmonary disease (COPD)in Western countries, but there is no such evidence for resource-limited countries. This study aimed to evaluate the cost-utility of SITT compared with multiple inhaler triple therapy (MITT) for COPD in Thailand.Methods A Markov model with a lifetime horizon from a societal perspective was conducted with seven health states, including moderate, severe and very severe, with and without acute exacerbation (AE) and death. Two SITTs, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR), were compared with MITT (salmeterol/fluticasone propionate with tiotropium (SAL/FP+TIO). A comprehensive literature review was performed to identify inputs. A quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed.Results FF/UMEC/VI could improve QALY by 0.014 with an increased lifetime cost of 25 649 Thai baht (THB) ($727) compared with SAL/FP+TIO. In contrast, BUD/GLY/FOR had a lower QALY of −0.007 with an increased total lifetime cost of 34,151 THB ($968). The ICER for FF/UMEC/VI was 1,899,408 THB/QALY ($53,823), while BUD/GLY/FOR was dominated by SAL/FP+TIO. Probabilistic sensitivity analysis indicated that FF/UMEC/VI had a 1.1% chance of being cost-effective at the threshold of 160,000 THB ($4,533). We found that a 30% reduction in FF/UMEC/VI price could lead to a cost-effective option.Conclusion Our study indicated that SITTs are not cost-effective at the current price compared with the current MITT for COPD treatment. However, FF/UMEC/VI could be a promising option, with an approximately 30% price reduction.