OBJECTIVES: To evaluate the relative efficacy of indacaterol 150µg + tiotropium 18µg (IND/TIO) versus triple therapies (i.e. tiotropium plus a fixed-dose combination [FDC] of a long-acting beta2-agonist [LABA] and inhaled corticosteroid [ICS]), a LABA/ICS FDC alone, and monotherapies, including indacaterol, tiotropium, aclidinium, salmeterol, formoterol, and placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD) in terms of trough FEV1 at 12 weeks. METHODS: Several of the treatments to be compared include ICS as part of the study treatment. Therefore the evidence base was restricted to RCTs not allowing for concomitant ICS use (for Novartis studies subgroup data for non-ICS users were included). For this population 23 RCTs were identified based on a systematic literature review, which were analysed simultaneously using a Bayesian network meta-analysis. Treatment-by-covariate interactions were included for the proportion of current-smokers to improve similarity of the trials. RESULTS: IND/TIO resulted in a higher change from baseline (CFB) in FEV1 by 0.24L (95%CrI: 0.20, 0.27) versus placebo at 12 weeks. IND/TIO is likely to be favourable versus salmeterol/fluticasone 50/500µg + tiotropium 18µg [difference 0.03L (95%CrI: -0.01, 0.07); probability better: 94%] and comparable to formoterol/budesonide 9/320µg + tiotropium 18µg [difference 0.02L (95%CrI: -0.02, 0.06); probability better: 80%]. IND/TIO has a larger CFB than the FDCs alone with an advantage of 0.07L (95%CrI: 0.03, 0.12) to 0.09L (95%CrI: 0.04, 0.15). IND/TIO also has a higher CFB than the monotherapies assessed. Out of the 13 regimens evaluated, there is a 77% probability that IND/TIO is the most efficacious treatment in terms of CFB in FEV1. Results were not sensitive to adjustment for smokers or to the exclusion of RCTs with concomitant anticholinergics or an exacerbation history. CONCLUSIONS: IND/TIO is expected be comparable to triple therapies and more efficacious than FDCs and monotherapies in terms of FEV1 at 12 weeks.