Background: Among patients with ST-segment elevation myocardial infarction (STEMI), rapid reperfusion is associated with improved mortality. As such, door-to-needle (D2N) and door-to-balloon (D2B) times have become metrics of quality of care and targets for intense quality improvement. Methods: The National Registry of Myocardial Infarction (NRMI) collected data regarding reperfusion therapy, its timing and in-hospital mortality among STEMI patients from 1990 through 2006. Results: Since 1990, NRMI has enrolled 1,374,232 STEMI patients at 2,157 hospitals. Among those, 774,279 (56.3%) were eligible for reperfusion upon arrival. The proportion receiving fibrinolytic therapy fell from 52.5% in 1990 to 27.6% in 2006 (P < .001), while the proportion undergoing primary percutaneous coronary intervention (pPCI) increased from 2.6% to 43.2%. Among reperfusion-eligible patients who received fibrinolytic therapy, there was a nearly linear decline in median D2N time from 59 minutes in 1990 to 29 minutes in 2006 (P < .001 for trend) as well as a decrease in mortality from 7.0% in 1994 to 6.0% in 2006 (P < .001). Among those undergoing pPCI, D2B time among nontransfer patients declined linearly from 111 minutes in 1994 to 79 minutes in 2006 (P < .001) with a decline in mortality from 8.6% to 3.1% (P < .001). The relative improvement in mortality attributable to improvements in D2N time was 16.3% and to D2B time was 7.5%. Conclusions: Since 1990, there has been a progressive decline in D2N and D2B time among reperfusion-eligible STEMI patients. These improvements have contributed, at least in part, to a progressive decline in mortality. © 2008 Mosby, Inc. All rights reserved.