OBJECTIVES:  To examine various algorithms for estimating costs from claims data associated with chronic obstructive pulmonary disease (COPD) exacerbations. METHODS:  The sample included COPD patients aged ≥40 years from a large US claims database who initiated long-acting bronchodilator monotherapy between 1/1/2008 and 1/31/2015. COPD exacerbations, associated costs, and all-cause costs (2015 consumer price index-adjusted) were ascertained in the one year prior to treatment initiation. Exacerbation events were defined as a COPD-related inpatient stay; emergency department (ED) visit; or an ambulatory visit followed by systemic corticosteroid or antibiotic use within 10 days. Exacerbation episodes consisted of multiple events, and continued until 14 days without an event. Exacerbation costs were defined by four algorithms: 1) COPD-related costs between episode start and end dates; 2) including COPD-related costs within 7 days following the end date; 3) including COPD-related costs within 14 days following the end date; 4) algorithm 3 plus costs for diagnostic work-up procedures (e.g. pulmonary imaging, spirometry) and breathing assistance (e.g., oxygen, ventilation). RESULTS:  The analysis included 27,394 patients; mean±SD age 68±10 years; 50% female; and 60% on Medicare. During the observation period, 43% of patients experienced ≥1 exacerbation and 15% had ≥1 exacerbation leading to an inpatient stay. All-cause and COPD-related mean±SD monthly costs were $1543±$2695 and $592±$1831, respectively. Mean±SD monthly COPD-exacerbation costs according to each algorithm were: 1) $190±$735; 2) $207±$800; 3) $216±$828; 4) $245±$1116. Mean±SD monthly severe-exacerbation (inpatient or ED) costs were: 1) $151±$703; 2) $157±$725; 3) $162±$745; 4) $187±$1040. CONCLUSIONS:  Depending on the algorithm, COPD exacerbations accounted for 32% to 41% of COPD-related costs and 12% to 16% of all-cause costs. COPD-related exacerbation costs were estimated to be nearly 30% higher with the broadest algorithm compared with the most conservative algorithm. Severe exacerbations accounted for 75% to 80% of COPD-related exacerbation costs.