Fibrinolytic therapy remains the most common reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI), particularly in smaller centers. Previous studies evaluated the relationship between time to treatment and outcomes when few patients were treated within 30 minutes of hospital arrival and many did not receive modern adjunctive medications. To quantify the impact of delay in door-to-needle time on mortality in a recent and representative cohort of STEMI patients, we analyzed a cohort of 62,470 STEMI patients treated with fibrinolytic therapy at 973 hospitals that participated in the National Registry of Myocardial Infarction from 1999-2002. We employed hierarchical models to evaluate the independent effect of door-to-needle time on inhospital mortality. In-hospital mortality was lower with shorter door-to-needle times (2.9% for ≤30 minutes, 4.1% for 31-45 minutes, and 6.2% for >45 minutes; p< 0.001 for trend). Compared with those experiencing door-to-needle times ≤30 minutes, the adjusted odd ratios (OR) of dying were 1.17 (confidence interval (CI) 1.04-1.31) and 1.37 (CI 1.23-1.52; p for trend <0.001) for those patients with door-to-needle times of 31-45 minutes and >45 minutes, respectively. This relationship