There is controversy regarding in-hospital mortality, revascularization, and other adverse outcomes in patients with ST-segment elevation (STEMI) and chronic obstructive pulmonary disease (COPD). We queried the 2003 to 2011 Nationwide Inpatient Sample databases to identify patients aged ≥18 years with a primary diagnosis of STEMI. Univariate and multivariate analyses were performed to evaluate the association of COPD with in-hospital clinical outcomes. Patients with COPD comprised 13.2% of 2,120,005 patients with STEMI. COPD was associated with older age, Medicare insurance, greater co-morbidities, and lower socioeconomic status. Compared with non-COPD patients, patients with COPD had higher inpatient mortality even after adjustment for multiple potential other factors (12.5% vs 8.6%, adjusted odds ratio [AOR] 1.13, 95% CI 1.11 to 1.15, p <0.001). Patients with COPD were more likely to develop new-onset heart failure (AOR 2.01, 95% CI 1.99 to 2.03), cardiogenic shock (AOR 1.24, 95% CI 1.22 to 1.26), and acute respiratory failure (AOR 2.46, 95% CI 2.43 to 2.50) during their hospital stay. Patients with COPD were less likely to undergo diagnostic angiographies and any revascularization procedures. The mean length of stay (6.0 vs 4.6 days; p <0.001) was greater in patients with COPD, as were hospital average hospital charges ($63,956 vs $58,536; p <0.001). In conclusion, among patients with STEMI, COPD is associated with a greater risk of in-hospital mortality, new-onset heart failure, acute respiratory failure, and cardiogenic shock.