Context: Understanding how door-to-drug and door-to-balloon times vary by time of day and day of week can inform the design of interventions to improve the timeliness of reperfusion therapy. Objective: To determine the pattern of door-to-drug and door-to-balloon times by time of day and day of week and whether this pattern may affect mortality. Design, Setting, and Participants: Cohort study of 68 439 patients with ST-segment elevation myocardial infarction(STEMI) treated with fibrinolytic therapy and 33 647 treated with percutaneous coronary intervention(PCI) from 1999 through 2002. We classified patient hospital arrival period into regular hours(weekdays, 7 AM-5 PM) and off-hours(weekdays 5 PM-7 AM and weekends). Main Outcome Measures: Geometric mean door-to-drug time for fibrinolytic therapy and door-to-balloon time for PCI and all-cause in-hospital mortality. All outcomes were adjusted for patient and hospital characteristics. Results: Most fibrinolytic therapy(67.9%) and PCI patients(54.2%) were treated during off-hours. Door-to-drug times were slightly longer during off-hours(34.3 minutes) than regular hours(33.2 minutes; difference, 1.0 minute; 95%confidence interval[CI], 0.7-1.4; P< .001). In contrast, door-to-balloon times were substantially longer during off-hours(116.1 minutes) than regular hours(94.8 minutes; difference, 21.3 minutes; 95%CI, 20.5-22.2; P< .001). A lower percentage of patients met guideline recommended times for door-to-balloon during off-hours(25.7%) than regular hours(47%; P< .001). Door-to-balloon times exceeding 120 minutes occurred much more commonly during off-hours(41.5%) than regular hours(27.7%; P< .001). Longer off-hours door-to-balloon times were primarily due to a longer interval between obtaining the electrocardiogram and patient arrival at the catheterization laboratory(off-hours, 69.8 minutes vs regular hours, 49.1 minutes; P< .001). This pattern was consistent across all hospital subgroups examined. Furthermore, patients presenting during off-hours had significantly higher adjusted in-hospital mortality than patients presenting during regular hours(odds ratio, 1.07; 95%CI, 1.01-1.14; P=.02). Conclusions: Presentation during off-hours was common and was associated with substantially longer times to treatment for PCI but not for fibrinolytic therapy. To achieve the best outcomes, hospitals providing PCI during off-hours should commit to doing so in a timely manner. Context: Understanding how door-to-drug and door-to-balloon times vary by time of day and day of week can inform the design of interventions to improve the timeliness of reperfusion therapy. Objective: To determine the pattern of door-to- drug and door-to-balloon times by time of day and day of week and whether this pattern may affect mortality. Design, Setting, and Participants: Cohort study of 68 439 patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy and 33 647 treated with percutaneous coronary intervention (PCI) from 1999 through 2002. We classified patient hospital arrival period into regular hours (weekdays, 7 AM-5 PM) and off-hours (weekdays 5 PM-7 AM and weekends). Main Outcome Measures: Geometric mean door-to-drug time for fibrinolytic therapy and door-to-balloon time for PCI and all-cause in-hospital mortality. All outcomes were adjusted for patient and hospital characteristics. Results: Most fibrinolytic therapy (67.9 %) and PCI patie Door-to-drug times were slightly longer during off-hours (34.3 minutes) than regular hours (33.2 minutes; difference, 1.0 minute; 95% confidence interval [CI] -1.4; P <.001). In contrast, door-to-balloon times were substantially longer during off-hours (116.1 minutes) than regular hours (94.8 minutes; difference, 21.3 minutes; 95% CI, 20.5-22.2; P <.001). A lower percentage of patients with guideline recommended times for door-to-balloon during off-hours (25.7%) than regular hours (47%; P <.001). Door-to- Longer off-hours door-to-balloon times were in a longer interval between obtaining the electrocardiogram and patient arrival at [41.5%] than regular hours (27.7%; P <.001) the catheterization laboratory (off-hours, 69.8 minutes vs regular hours, 49.1 minutes; P <.001). This pattern was consistently across all hospital subgroups examined. Furthermore, patients presenting during off-hours had significantly higher in-hospital mortality than patients presenting during regular hours (odds ratio, 1.07; 95% CI, 1.01-1.14; P = .02). Conclusions: Presentation during off-hours was common and was associated with substantially longer times to treatment for PCI but not for fibrinolytic therapy. To achieve the best outcomes, hospitals provide PCI during off-hours should commit to doing so in a timely manner.