OBJECTIVES:  Exacerbations are important drivers of COPD-related costs and have been shown to increase mortality, as well as decrease health-related quality of life in COPD-patients. Tiotropium (TIO) is a long-acting anticholinergic (LAMA) and a well-established bronchodilator for the treatment of moderate to very severe COPD. Evidence from a recent head-to-head trial, SPARK, suggests that TIO is superior to glycopyrronium (GLY) in preventing severe exacerbations. This study assessed the cost-effectiveness of TIO versus GLY for France making use of this new clinical evidence. METHODS:  Treatment efficacy was modelled in a Markov cohort model as improvements in lung function, quality-adjusted life years and as a lowering of the risk of exacerbations (rate of exacerbations), by using best available clinical data for moderate to very severe (GOLD II – IV) COPD from the UPLIFT and SPARK trials. Mortality and cost inputs were obtained from relevant sources in France. Health and cost outcomes (€ 2011) were simulated over an approximate life time horizon, starting from an age of 65 years and considering a societal perspective without indirect costs. Robustness of results was validated in deterministic sensitivity analyses. RESULTS:  Over a life time horizon, TIO resulted in an incremental cost of €2,138 and generated a better health outcome of 0.18 in incremental QALYs compared to GLY for the average COPD patient. The cost per QALY gained (ICER) was €11,880. The main driver of results was the relative risk of severe exacerbations found in SPARK (RR GLY/TIO: 1.43 CI 1.05-1.97, P = 0.025). CONCLUSIONS:  The results from this study show that TIO may be considered as a cost-effective treatment in moderate to very severe COPD in France. The findings were to a large extent driven by TIO being relatively efficacious in preventing severe exacerbations, based on the outcomes in the SPARK trial.