BACKGROUND Development of ventricular fibrillation or pulseless ventricular tachycardia after an initial rhythm of pulseless electrical activity or asystole is associated with significantly increased cardiac arrest mortality. OBJECTIVE To examine differences in epinephrine administration during cardiac arrest between patients who had a secondary ventricular fibrillation or ventricular tachycardia develop and patients who did not. METHODS Data were collected for 2 groups of patients with in-hospital cardiac arrest and an initial rhythm of pulseless electrical activity or asystole: those who had a secondary ventricular fibrillation or ventricular tachycardia develop (cases) and those who did not (controls). Dosing of epinephrine during cardiac arrest and other variables were compared between cases and controls. RESULTS Of the 215 patients identified with an initial rhythm of pulseless electrical activity or asystole, 51 (23.7%) had a secondary ventricular fibrillation or ventricular tachycardia develop. Throughout the total duration of arrest, including periods of return of spontaneous circulation, the dosing interval for epinephrine in patients who had a secondary ventricular fibrillation or ventricular tachycardia develop was 1 mg every 3.4 minutes compared with 1 mg every 5 minutes in controls (P= .001). For the total duration of pulselessness, excluding periods of return of spontaneous circulation during the arrest, the dosing interval for epinephrine in patients who had a secondary ventricular fibrillation or ventricular tachycardia develop was 1 mg every 3.1 minutes versus 1 mg every 4.3 minutes in controls (P= .001). CONCLUSIONS More frequent administration of epinephrine during cardiac arrest is associated with development of secondary ventricular fibrillation or ventricular tachycardia.