Reducing door-to-balloon (D + B) time during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) reduces mortality. Prehospital 12-lead electrocadiography (ECG) with cardiac catheterization laboratory (CCL) activation may reduce D + B time. Paramedic-performed ECG was initiated in the city of San Diego in January 2005 with STEMI diagnosis based on an automated computer algorithm. We undertook this study to determine the effect of prehospital CCL activation on D + B time for patients with acute STEMI brought to our institution. All data were prospectively collected for patients with STEMI including times to treatment and clinical outcomes. We evaluated 78 consecutive patients with STEMI from January 2005 to June 2006, and the study group consisted of all patients with prehospital activation of the CCL (field STEMI; n = 20). The control groups included concurrently-treated patients with STEMI during the same period who presented to the emergency department (nonfield STEMI; n = 28), and all patients with STEMI treated in the preceding year (2004) (historical STEMI; n = 30). Prehospital CCL activation significantly reduced D + B time (73 +/- 19 minutes field STEMI, 130 +/- 66 minutes nonfield STEMI, 141 +/- 49 minutes historical STEMI; p <0.001) with significant reductions in door-to-CCL and CCL-to-balloon times as well. The majority of patients with field STEMI achieved D + B times of <90 minutes (80% field STEMI, 25% nonfield STEMI, 10% historical STEMI; p <0.001). In conclusion, this study demonstrates that prehospital electrocardiographic diagnosis of STEMI with activation of the CCL markedly reduces D + B time.