Purpose: This study assessed therapy persistence in patients with chronic obstructive pulmonary disease (COPD) in France, and the impact of non-persistence on exacerbations and described COPD-related healthcare resource use (HRU). Methods: Patients aged ≥45 years who received ≥1 dispensed bronchodilator per quarter over three consecutive quarters between 2007 and 2014 and initiated specific COPD therapy were selected from the Echantillon Généraliste des Bénéficiaires (EGB) database. Persistence, defined as the absence of dispensing gaps of >90 days, was measured at 12 months. Exacerbations were compared between persistent and non-persistent patients during follow-up after patient matching and adjustment for confounding factors. COPD-related HRU during follow-up was described. Results: Among 4020 patients with COPD, 2164 initiated a specific therapy. Of these, 54.4% stopped treatment within 12 months. Persistence with all COPD therapy regimens was low, particularly for inhaled corticosteroid (ICS; 25.6%) and ICS/twice-daily long-acting beta-agonist (39.4%) regimens. Among 721 persistent patients who were matched with 721 non-persistent patients, there was no difference in the number of moderate or severe exacerbations at 12 months. However, medical procedures (for instance, pulmonary function testing and chest X-rays) were more frequently observed among persistent patients than among nonpersistent patients, suggesting worse disease severity. Conclusion: Patients receiving specific treatment(s) for COPD demonstrated low persistence for all examined therapy regimens, with no clear impact of persistence status on the frequency of exacerbations at 12 months.