PurposeWhether inhaled medications improve long‐term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5‐year survival in COPD.MethodsA population‐based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006–2009 were enrolled. Inhaled drug daily use during 5‐year follow‐up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time‐dependent exposure were identified: (i) long‐acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio‐demographic, comorbidities, drug use) and time‐dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed.ResultsA total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow‐up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43–1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79–0.99).ConclusionsThese findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate–severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.