To estimate annual drug wastage (drug that is discarded without being administered to a patient) and associated costs incurred by a typical hospital due to the use of multi-unit-dose packaged COPD treatment devices in patients admitted for acute chronic obstructive pulmonary disease (COPD) exacerbation. An economic model was built to evaluate the annual number of wasted doses and related costs associated with adult patients admitted to the hospital for an acute COPD exacerbation. Model inputs were based on a retrospective study of adults with COPD admitted to a university-affiliated hospital between January 2011 and June 2012 (Sakaan, Am J Respir Crit Care Med. 2014). Wasted doses for the following comparators were assessed: albuterol, arformoterol, fluticasone, formoterol, ipratropium, tiotropium, budesonide/formoterol, and fluticasone/salmeterol (all non-nebulized formulations except arformoterol). Because arformoterol is available in a single-unit-dose package, no wastage was assumed. Pharmacy costs of wasted doses were calculated from number of doses wasted and publicly available wholesale acquisition cost per dose (Red Book™, 2014). Based on a hospital with 500 COPD admissions per year, the estimated annual number of wasted doses was 18,045 (87%) at a cost of $69,103. Budesonide/formoterol, tiotropium, and fluticasone/salmeterol were most costly, representing an annual cost of $28,292, $17,686, and $17,366 in drug wastage, respectively. Arformoterol ($0), formoterol ($518), and fluticasone ($550) had the lowest annual drug wastage costs. The highest drug wastage costs per patient were with fluticasone ($195) and budesonide/formoterol ($161), while the lowest drug wastage costs per patient were with arformoterol ($0) and albuterol ($17). For patients admitted to the hospital with a COPD exacerbation, the use of multi-unit-dose packaged devices may result in significant costs due to drug wastage that could be avoided with use of single-unit-dose packaged devices.