OBJECTIVES: Very little is known about severe Chronic Obstructive Pulmonary Disease (COPD) exacerbations among patients with Alpha-1 Antitrypsin Deficiency (AATD). We assessed inpatients with AATD and COPD among a sample of COPD inpatients to ascertain demographic, clinical and economic differences in the course of disease and treatment. METHODS: Using data from the 2009 Nationwide Inpatient Sample (NIS), we identified COPD (ICD-9-CM: 491.xx, 492.xx, or 496.xx) patients with AATD (273.4). We compared patient demographics and healthcare outcomes (e.g., length of stay, inpatient death, type and number of procedures, and cost of care) between COPD patients with and without alpha-1 antitrypsin deficiency. Frequencies and percentages for patient demographics were compared using bivariate statistics (e.g., chi-square test). Recognizing the non-parametric nature of length of stay and cost, we calculated median values and interquartile ranges for these variables for each group of patients. Finally, the risk of inpatient death was estimated using logistic regression. RESULTS: Of 840,242 patients with COPD (10.8% of the NIS sample population), 0.08% (684) had a primary or secondary diagnosis code for AATD. COPD+AATD were younger (56 vs 70, p<0.0001) and as a result, less likely to be covered by Medicare (57% vs 72%, p<0.0001).  AATD patients were also more likely to have comorbid non-alcoholic liver disease (7% vs 2%, p<0.0001), depression (17% vs 13%, p=0.0328), and pulmonary circulation disorders (7% vs 4%, p=0.0299). Patients with AATD had a 14% longer length of stay (IRR = 1.14, 95%CI 1.07, 1.21) and cost $1,487(p=0.0251) more than COPD inpatients without AATD. CONCLUSIONS: AATD is associated with increased length of stay and cost, as well as higher frequency of comorbid non-alcoholic liver disease, depression, and pulmonary circulation disorders. Future research should assess other differences between AATD and the general COPD population such as natural history of disease, treatment responsiveness and disease progression.