OBJECTIVES: Cardiovascular (CV) disease significantly contributes to morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients; however, the economic burden of acute CV events in this population is still unknown. Our objective was to estimate the direct medical costs associated with the development of acute CV events in patients with COPD.   METHODS: We identified patients with a COPD diagnosis (ICD-9 491.x, 492.x, 496.x) between 2005-2010 in the IMS LifeLink Health Claims Database. Patients experiencing an incident CV event (MI, ACS, CHF, arrhythmia, or stroke) resulting in an ER visit or inpatient admission (case index) were matched to up to 3 controls on age, region, gender, year of COPD diagnosis, and time between COPD diagnosis and index date. Mean costs (total, inpatient, outpatient, and pharmacy) in the 12 months before and after the case index and control index were compared, with total costs attributable to the incident CV event determined by using a difference in differences regression to adjust for patient comorbidities. RESULTS: Among 9,537 case and 26,128 control patients, the average age was 69.1 years and 51% were male. Hypertension, diabetes, and coronary atherosclerosis were the most prevalent comorbidities. Total costs were $27,300 and $15,016 (pre-index), and $51,468 and $15,596 (post-index) for cases and controls, respectively. Regression analysis resulted in an adjusted difference in differences value of $23,601 (p<0.001). As a percentage of total costs, pharmacy and outpatient costs decreased between the pre-index and post-index periods (13% to 8% and 28% to 22%), while inpatient costs increased (59% to 69%); percentages for control patients remained unchanged. CONCLUSIONS: The development of acute CV events in COPD patients is associated with a large increase in direct medical costs, predominantly driven by inpatient costs. Interventions aimed at reducing the incidence of acute CV events in this population are needed to mitigate overall cost burden.