Copyright © 2016 by the American Thoracic Society. Rationale: Hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and health care costs, and hospitals in the United States are now penalized by the Centers for Medicare and Medicaid Services for excessive readmissions. Identifying patients at risk of readmission is important, but modifiable risk factors have not been clearly established, and the potential contributing role of psychological disease has not been examined adequately. We hypothesized that depression and anxiety would increase the risk of both short-and long-term readmissions for acute exacerbation of COPD. Objectives: To characterize the associations between depression and anxiety and COPD readmission risk. Methods: We examined the medical records for all patients with a primary diagnosis of acute exacerbation of COPD by International Classification of Diseases, Ninth Revision codes admitted to the University of Alabama at Birmingham Hospital between November 2010 and October 2012. Those who did not meet the standardized study criteria for acute exacerbation of COPD and those with other respiratory illnesses as the primary diagnosis were excluded. Comorbidities were recorded on the basis of physician documentation of the diagnosis and/or the use of medications in the electronic medical record. Multivariable regression analyses identified factors associated with readmission for acute exacerbation of COPD at 1 year and within 30 and 90 days. Measurements and Main Results: Four hundred twenty-two patients were included, with 132 readmitted in 1 year. Mean age was 64.8611.7 years, andmean percentpredicted FEV1 was 48.1618.7%. On univariate analysis, readmitted patients had lower percent predicted FEV1 (44.9617.3%vs. 50.2619.4%; P = 0.05) and a higher frequency of depression(47.7%vs. 23.4%;P,0.001).Onmultivariable analysis, 1-year readmission was independently associated with depression (adjusted odds ratio [OR], 2.67; 95% confidence interval [CI], 1.59-4.47) and in-hospital tobacco cessation counseling (adjusted OR, 0.34; 95% CI, 0.18-0.66). Depression also predicted readmission at 30 days (adjusted OR, 3.83; 95% CI, 1.84-7.96) and 90 days (adjusted OR, 2.47; 95% CI, 1.34-4.55). Conclusions: Depression is an independent risk factor for both short-and long-term readmissions for acute exacerbation of COPD and may represent a modifiable risk factor. In-hospital tobacco cessation counseling was also associated with reduced 1-year readmission.