The use of polyunsaturated fatty acids of the .omega.-3 series such as eicosapentaenoic acid (EPA, C.sub.20:5 .omega.-3), docosahexaenoic acid (DHA, C.sub.22:6 .omega.-3), or their pharmaceutically acceptable derivatives is described for the primary prevention of major cardiovascular events in subjects who have not undergone previous infarct episodes.