Drug-eluting stents (DESs) are used in >80% of percutaneous coronary intervention (PCI) procedures; however, up to 2/3 are used for off-label indications. Factors associated with DES use in patients with ST-elevation myocardial infarction (STEMI) are not known in contemporary clinical practice. We analyzed temporal trends, geographic patterns, and sociodemographic factors associated with off-label use of DESs in patients undergoing primary PCI for STEMI from July 2004 to March 2006 in the National Cardiovascular Data Registry (NCDR). The main outcome of this study was receipt of any DES, and the candidate independent variables were sociodemographic, hospital, clinical, and procedural variables. We also analyzed temporal trends and geographic patterns for use of DESs. A total of 30,235 patients with STEMI underwent primary PCI with use of DESs (84%) or bare metal stents (16%). Adoption of DESs was rapid but varied widely as a function of geographic location. After adjusting for clinical and procedural variables, older age was associated with lower use (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.91 to 0.98), whereas white race (OR 1.14, 95% CI 1.03 to 1.27), commercial insurance (OR 1.22, 95% CI 1.11 to 1.34), and the west census region (OR 1.37, 95% CI 1.04 to 1.81) were associated with higher use of DESs. In conclusion, adoption of DESs was rapid in patients with STEMI, but geographic location and sociodemographic and hospital factors were associated with the use DESs.