Background More than 20 randomized trials and 4 meta-analyses have been conducted on the use of prophylactic lidocaine in acute myocardial infarction (MI). The results suggest that lidocaine reduces ventricular fibrillation (VF) but increases mortality rates in acute MI. Methods and Results Patients with ST-elevation MI who were examined <6 hours after symptom onset (n = 903) were randomly assigned to either lidocaine or no lidocaine and to either streptokinase and heparin or heparin alone. Lidocaine was given as 4 boluses of 50 mg each every 2 minutes, then an infusion of 3 mg/min for 12 hours, then 2 mg/min for 36 hours. We compared the incidence of in-hospital death and ventricular arrhythmias. We then performed a meta-analysis of prophylactic lidocaine in acute MI that included these and prior trial results. The rates of VF and death with and without lidocaine were calculated for each trial, then odds ratios (OR) with confidence intervals (CI) were calculated for the risk of these events overall with and without lidocaine. Patients given lidocaine in the randomized study had significantly less VF (2.0% vs 5.7% without lidocaine, P = .004) and a trend toward increased mortality rates (9.7% vs 7.0%, P = .145). Meta-analysis revealed nonsignificant trends toward reduced VF (OR 0.71, 95% CI 0.47 to 1.09) and increased mortality rates (OR 1.12, 95% CI 0.91 to 1.36) with lidocaine. Conclusions Lidocaine reduces VF but may adversely affect mortality rates. The routine use of prophylactic lidocaine in acute MI is not recommended. (Am Heart J 1999;137:792-8.)