Background: Cardiovascular disease is a major cause of death in patients with chronic obstructive pulmonary disease (COPD) and predicts hospitalisation for acute exacerbation, in-hospital death and post-discharge mortality. Although β blockers improve cardiovascular outcomes, patients with COPD often do not receive them owing to concerns about possible adverse pulmonary effects. There are no published data about β blocker use among inpatients with COPD exacerbations. A study was undertaken to identify factors associated with β blocker use in this setting and to determine whether their use is associated with decreased in-hospital mortality. Methods: Administrative data from the University of Alabama Hospital were reviewed and patients admitted between October 1999 and September 2006 with an acute exacerbation of COPD as a primary diagnosis or as a secondary diagnosis with a primary diagnosis of acute respiratory failure were identified. Demographic data, comorbidities and medication use were recorded and subjects receiving β blockers were compared with those who did not. Multivariate regression analysis was performed to determine predictors of in-hospital death after controlling for known covariates and the propensity to receive β blockers. Results: 825 patients met the inclusion criteria. In-hospital mortality was 5.2%. Those receiving β blockers (n = 142) were older and more frequently had cardiovascular disease than those who did not. In multivariate analysis adjusting for potential confounders including the propensity score, β blocker use was associated with reduced mortality (OR = 0.39; 95% CI 0.14 to 0.99). Age, length of stay, number of prior exacerbations, the presence of respiratory failure, congestive heart failure, cerebrovascular disease or liver disease also predicted in-hospital mortality (p<0.05). Conclusions: The use of β blockers by inpatients with exacerbations of COPD is well tolerated and may be associated with reduced mortality. The potential protective effect of β blockers in this population warrants further study.