Polyunsaturated fatty acids (PUFAs) have been suggested for cardiovascular health. This study was conducted to investigate the prognostic impacts of the PUFA metabolites, oxylipins, on clinical outcomes in coronary artery disease (CAD). A total of 2,239 patients with stable CAD were prospectively enrolled and followed up regularly. Among them, twenty-five consecutive patients with new onset of acute myocardial infarction (AMI) within 2-year follow-up were studied. Another 50 gender- and age-matched patients without clinical cardiovascular events for more than 2 years were studied for control. Baseline levels of specific arachidonic acid metabolites were significantly higher in patients with subsequent AMI than in the controls. In Kaplan-Meier analysis, the incidence of future AMI was more frequently seen in patients with higher baseline levels of 8-hydroxyeicosatetraenoic acid (HETE), 9-HETE, 11-HETE, 12-HETE, 15-HETE, 19-HETE, 20-HETE, 5,6-epoxyeicosatrienoic acid (EET), 8,9-EET, 11,12-EET, or 14-15-EET when compared to their counterparts (all the P < 0.01). Further, serum levels of these specific HETEs, except for 11,12-EET, were positively correlated to the levels of some inflammatory and cardiac biomarker such as tumor necrosis factor-α and N-terminal pro B-type natriuretic peptide. Accordingly, serum specific oxylipins levels are increased and associated with the consequent onset of AMI, suggesting their potential role for secondary prevention in clinically stable CAD.