Kirsten Koehorst-ter Huurne,1 Sharina Kort,1 Job van der Palen,1,3 Wendy JC van Beurden,1 Kris LL Movig,2 Paul van der Valk,1 Marjolein Brusse-Keizer1 1Department of Pulmonary Medicine, 2Department of Clinical Pharmacy, Medisch Spectrum Twente, 3Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands Background: Poor adherence to inhaled medications in COPD patients seems to be associated with an increased risk of death and hospitalization. Knowing the determinants of nonadherence to inhaled medications is important for creating interventions to improve adherence. Objectives: To identify disease-specific and health-related quality of life (HRQoL) factors, associated with adherence to inhaled corticosteroids (ICS) and tiotropium in COPD patients. Methods: Adherence of 795 patients was recorded over 3 years and was deemed optimal at >75%–≤125%, suboptimal at ≥50%–125% (overuse). Health-related quality of life was measured with the Clinical COPD Questionnaire and the EuroQol-5D questionnaire. Results: Patients with a higher forced expiratory volume in 1 second (FEV1)/vital capacity (VC) (odds ratio [OR] =1.03) and ≥1 hospitalizations in the year prior to inclusion in this study (OR =2.67) had an increased risk of suboptimal adherence to ICS instead of optimal adherence. An increased risk of underuse was predicted by a higher FEV1/VC (OR =1.05). Predictors for the risk of overuse were a lower FEV1 (OR =0.49), higher scores on Clinical COPD Questionnaire-question 3 (anxiety for dyspnea) (OR =1.26), and current smoking (OR =1.73). Regarding tiotropium, predictors for suboptimal use were a higher FEV1/VC (OR =1.03) and the inability to perform usual activities as asked by the EuroQol-5D questionnaire (OR =3.09). A higher FEV1/VC also was a predictor for the risk of underuse compared to optimal adherence (OR =1.03). The risk of overuse increased again with higher scores on Clinical COPD Questionnaire-question 3 (OR =1.46). Conclusion: Several disease-specific and quality of life factors are related to ICS and tiotropium adherence, but a clear profile of a nonadherent patient cannot yet be outlined. Overusers of ICS and tiotropium experience more anxiety. Keywords: chronic obstructive pulmonary disease, adherence, inhalation medication, quality of life