OBJECTIVES: The Canadian Thoracic Society (CTS) guidelines for the management of Chronic Obstructive Pulmonary Disease (COPD) recommend incorporating combination therapy [long-acting B2METHODS: Using clinical guidelines and current management of COPD as the basis for the analysis, a markov model was constructed to determine, from a health systems perspective, the cost-effectiveness of combination therapy versus LABA alone between four treatment strategies: 1) maintenance therapy for all patients using LABA alone (base case); and in addition to the base case; 2) provide combination therapy for severe cases (forced expiratory volume in 1 second [FEV1]<35% predicted); 3) provide combination therapy for moderate or severe cases (FEV1<50% predicted); and 4) provide combination therapy for all COPD patients. Estimates of mortality, exacerbation and disease progression rates, and outcomes (QALY) were derived from a systematic review of the literature. Cost estimates were based on current Alberta health care costs. A time horizon of 3 years was used. RESULTS: Beginning with the lowest cost intervention of LABA for all cases: the incremental cost-effectiveness ratio (ICER) of providing combination therapy for severe patients was $6566 per QALY gained. The marginal ICER for providing combination therapy for moderate and severe cases was $25,979 per QALY gained and providing combination therapy for all stages of disease was $232,870 per QALY gained. CONCLUSION: It would be cost-effective to provide combination therapy for moderate and severe COPD patients. This analysis has significant implications for the planned revision of CTS guidelines because it promotes the wider use of combination therapy in COPD populations with greater severity.