The efficacy of lidocaine to prevent ventricular fibrillation during the prehospital phase of suspected acute myocardial infarction was assessed 3 hours after administration in a randomized controlled trial. A total of 204 patients examined within 6 hours after onset of symptoms were included, and acute myocardial infarction was later confirmed in 63% of these. Lidocaine, administered as a 100 mg intravenous bolus dose followed by a 300 mg intramuscular injection, failed to prevent ventricular fibrillation, which was observed in 2 (2.1%) of 96 patients in the lidocaine group and in 3 (3.0%) of 101 patients in the placebo group (p = 0.95; odds ratio 0.7, 95% confidence interval 0.4 to 1.3). In addition, sudden cardiac collapse with unknown heart rhythm was observed in three patients who received lidocaine (3.1%) compared with none in the placebo group (p = 0.23; odds ratio 7.6, 95% confidence interval 2.8 to 22.1). The results of this small study suggest that lidocaine, even when given in a high dose, is ineffective in preventing ventricular fibrillation when administered before hospitalization for suspected acute myocardial infarction. Prophylactic use of lidocaine in this situation may therefore not be warranted or advisable.