Timely reperfusion after ST-elevation myocardial infarction (STEMI) improves survival. Guidelines recommend primary percutaneous coronary intervention (PPCI) within 90 minutes of arrival at a PCI-capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer to a PCI-capable hospital is not feasible. We identified STEMI patients receiving reperfusion therapy at 229 hospitals participating in the Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) database (January 1, 2003 through December 31, 2008). Temporal trends in the use of fibrinolysis and PPCI, its timeliness, and in-hospital mortality outcomes were assessed. We also assessed predictors of fibrinolysis versus PPCI and compliance with performance measures. Defect-free care was defined as 100% compliance with all performance measures. We identified 29 190 STEMI patients, of whom 2441 (8.4%) received fibrinolysis; 38.2% of these patients achieved door-to-needle times ≤30 minutes. Median door-to-needle times increased from 36 to 60 minutes (P=0.005) over the study period. Among PPCI patients, median door-to-balloon times decreased from 94 to 64 minutes (P<0.0001) over the same period. In-hospital mortality was higher with fibrinolysis than with PPCI (4.6% vs 3.3%, P=0.001) and did not change significantly over time. Patients receiving fibrinolysis were less likely to receive defect-free care compared with their PPCI counterparts. Use of fibrinolysis for STEMI has decreased over time with concomitant worsening of door-to-needle times. Over the same time period, use of PPCI increased with improvement in door-to-balloon times. In-hospital mortality was higher with fibrinolysis than with PPCI. As reperfusion for STEMI continues to shift from fibrinolysis to PPCI, it will be critical to ensure that door-to-needle times and outcomes do not worsen.