OBJECTIVES: Hand-held (HH-LA) or nebulizer (Neb-LA) devices are traditionally used to deliver long-acting bronchodilators for maintenance treatment of COPD. However, a significant proportion of COPD patients with cardiovascular and neurological (CV&N) comorbidities may have low confidence in operating hand-held inhaler devices as instructed. This study compared patient-reported confidence and satisfaction with device use and their association with other PROs among COPD patients with ≥ 1 CV&N comorbidities treated with HH-LA or Neb-LA. METHODS: Data from 2015 Adelphi US Respiratory Disease Specific Programme, a nationally representative survey of physicians and their COPD patients were analyzed. Since HH-LA use is overrepresented in the COPD population, Neb-LA patients were oversampled (n=204) to augment the sample size. CV&N comorbidities included Alzheimer's, dementia, Parkinson's, cerebrovascular disease, congestive heart failure and coronary artery disease. PROs included - (i) confidence and satisfaction with inhaler device, ii) Morisky medication adherence scale (MMAS) and iii) COPD assessment test (CAT). Categorical and continuous outcomes variables were tested using chi-square and independent sample t-tests, respectively at P<0.05. RESULTS: Of 909 COPD patients, 28.7% had ≥1CV&N comorbidities (160/705 on HH-LA; 101/204 on Neb-LA). Baseline characteristics were comparable between patients treated with HH-LA or Neb-LA (n=261). A significantly higher proportion of Neb-LA than HH-LA patients in this sub-group reported being ‘very’ or ‘completely’ confident (73.7% vs. 55.2% p=0.034) and ‘very’ or ‘extremely’ satisfied (86.8% vs. 66.1%; p=0.01) with using their device. Greater confidence with use of Neb-LA in this sub-group were associated with better adherence, as reported on the MMAS (rho=0.30, p=0.02) but not CAT (0.04, p=0.75) scores. CONCLUSIONS: In this survey of COPD patients with cardiovascular or neurological comorbidities, use of Neb-LA was associated with greater patient reported confidence and satisfaction with device use as compared to treatment with HH-LA. Greater confidence was also associated with better adherence for Neb-LA patients.