The interval from the first alert of the healthcare system to the initiation of reperfusion therapy (system delay) is associated with mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI). The importance of system delay in patients treated with fibrinolysis versus pPCI has not been assessed. We obtained data on system delay from the Danish Acute Myocardial Infarction-2 study, which randomized 1,572 patients to fibrinolysis or pPCI. The study end points were 30-day and 8-year mortality. The short system delays were associated with reduced absolute mortality in both the fibrinolysis group (<1 hour, 5.6%; 1 to 2 hours, 6.9%; 2 to 3 hours, 9.5%; and >3 hours, 11.5%; test for trend, p = 0.08) and pPCI group (<1 hour, not assessed; 1 to 2 hours, 2.6%; 2 to 3 hours, 7.5%; >3 hours, 7.7%; test for trend, p = 0.02). The lowest 30-day mortality was obtained with pPCI and a system delay of 1 to 2 hours (vs fibrinolysis within <1 hour, adjusted hazard ratio 0.33; 95% confidence interval 0.10 to 1.10; p = 0.07; vs fibrinolysis within 1 to 2 hours, adjusted hazard ratio 0.37; 95% confidence interval 0.14 to 0.95; p = 0.04). pPCI and system delay >3 hours was associated with a similar 30-day and 8-year mortality as fibrinolysis within 1 to 2 hours. In conclusion, short system delays are associated with reduced mortality in patients with ST-segment elevation myocardial infarction treated with fibrinolysis as well as pPCI. pPCI performed with a system delay of <2 hours is associated with lower mortality than fibrinolysis performed with a faster or similar system delay.