Objectives: Studies investigating associations between chronic obstructive pulmonary disease (COPD) outcomes and psychiatric comorbidity have yielded mixed findings. We examined a national sample of hospitalized COPD patients to evaluate the impact of three psychiatric conditions on mortality and readmission. Methods: Department of Veterans Affairs (VA) administrative and laboratory data were used to identify; 26,591 consecutive patients admitted for COPD during October 2006 to September 2008. Associations between psychiatric comorbidity and both 30-day mortality and readmission were examined using generalized estimating equations and Cox proportional hazards regression, respectively, with adjustments for patient demographics, medical comorbidities, illness severity, and clustering within hospitals. Results: Unadjusted 30-day mortality was higher in patients with anxiety (5.3% vs. 3.8% [P < 0.001]) and depression (6.2% vs. 3.8% [<0.001]). In multivariable analyses, adjusted odds of 30-day mortality were higher for patients with depression (OR, 1.53; 95% CI, 1.28-1.82) and anxiety (OR, 1.72; 1.42 -2.10), but not for patients with PTSD (OR, 1.19; 0.92-1.55). Unadjusted 30-day readmission rates also varied by diagnosis; depression and PTSD were associated with lower rates of readmission (10.4% vs. 11.6% [<0.05] and 8.6% vs. 11.6% (<0.001], respectively), whereas anxiety was not (11.3% vs. 11.5% [NS]). However, after covariate adjustment using multivariable models, anxiety and depression (but not PTSD) were associated with increased risk for readmission (HR, 1.22; 1.03 -1.43 and HR, 1.35; 1.18 -1.54, respectively). Conclusion: Comorbid anxiety and depression may have an adverse impact on COPD hospital prognosis or may be indicative of more severe illness. (Psychosomatics 2011; 52:441-449)