This study compared monounsaturated oleic acid with n-6 and n-3 polyunsaturated fatty acids (PUFAs) for their ability to modify the vulnerability to cardiac arrhythmias during ischemia or reperfusion in rats. Replacement of saturated animal fat in the diet with oleic acid-rich olive oil did not significantly alter the incidence of ventricular fibrillation or other cardiac arrhythmias. Replacement with either n-6-rich sunflower seed oil or n-3-rich fish oil reduced the incidence and severity of arrhythmias occurring in ischemia. The fish oil significantly reduced reperfusion arrhythmias independently of antecedent ischemic arrhythmias. Fatal ventricular fibrillation was significantly reduced by n-6 (8%; n = 25) and n- 3 (0%; n = 24) PUFA but not by monounsaturates (36%; n = 25) compared with saturated fat (42%; n = 24). The results suggest that dietary replacement of saturated fats by n-6 and especially n-3 PUFA but not monounsaturated fatty acids can reduce the likelihood of an ischemic event leading to sudden cardiac death.