Timely reperfusion therapy is recommended for patients with ST-segment elevation myocardial infarction (STEMI), and door-to-balloon delay has been proposed as a performance measure in triaging patients for primary percutaneous coronary intervention (PCI). However, focusing on the time from first contact with the health care system to the initiation of reperfusion therapy (system delay) may be more relevant, because it constitutes the total time to reperfusion modifiable by the health care system. No previous studies have focused on the association between system delay and outcome in patients with STEMI treated with primary PCI. To evaluate the associations between system, treatment, patient, and door-to-balloon delays and mortality in patients with STEMI. Historical follow-up study based on population-based Danish medical registries of patients with STEMI transported by the emergency medical service and treated with primary PCI from January 1, 2002, to December 31, 2008, at 3 high-volume PCI centers in Western Denmark. Patients (N = 6209) underwent primary PCI within 12 hours of symptom onset. The median follow-up time was 3.4 (interquartile range, 1.8-5.2) years. Crude and adjusted hazard ratios of mortality obtained by Cox proportional regression analysis. A system delay of 0 through 60 minutes (n = 347) corresponded to a long-term mortality rate of 15.4% (n = 43); a delay of 61 through 120 minutes (n = 2643) to a rate of 23.3% (n = 380); a delay of 121 through 180 minutes (n = 2092) to a rate of 28.1% (n = 378); and a delay of 181 through 360 minutes (n = 1127) to a rate of 30.8% (n = 275) (P < .001). In multivariable analysis adjusted for other predictors of mortality, system delay was independently associated with mortality (adjusted hazard ratio, 1.10 [95% confidence interval, 1.04-1.16] per 1-hour delay), as was its components, prehospital system delay and door-to-balloon delay. System delay was associated with mortality in patients with STEMI treated with primary PCI.