The risk of CHD has been linked to n-3 and trans-fatty acids. The purpose of the present study was to evaluate the hypothesis that lower n-3 fatty acids and higher trans-fatty acids in erythrocytes are associated with an increased risk of acute non-fatal myocardial infarction (MI), and that fatty acid profiles can discriminate MI cases from controls. Fifty cases with acute non-fatal MI and fifty age- and sex-matched controls without MI were recruited. The Omega-3 Index (the sum of EPA and DHA in erythrocytes) was significantly lower in cases than controls (9·57 (sem 0·28) v. 11·81 (sem 0·35) %; P < 0·001), while total trans-fatty acids were significantly higher (1·01 (sem 0·04) v. 0·56 (sem 0·03) %; P < 0·001). The Omega-3 Index was associated with decreased risk of MI (OR 0·08 (95 % CI 0·02, 0·38); P = 0·001), while total trans-fatty acids were associated with an increased risk of MI (OR 72·67 (95 % CI 6·68, 790·74); P < 0·001). The area under the receiver operating characteristic curve of fatty acid profiles was larger than that for traditional risk factors, suggesting that fatty acid profiles make a higher contribution to the discrimination of MI cases from controls compared with modified Framingham risk factors. In conclusion, a higher Omega-3 Index and lower trans-fatty acids in erythrocytes are associated with a decreased risk of MI. Furthermore, fatty acid profiles improve discrimination of acute non-fatal MI compared with established risk factors.