Eicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. The aim of this study was to investigate the antiplatelet effect of EPA combined with acetylsalicylic acid (ASA) following stent implantation. Eighteen patients who had undergone coronary stent implantation at least 8 months previously were included. All patients were given EPA ethyl ester (EPA-E) 1.8 g/day in addition to ASA 100 mg/day for 12 weeks. After the treatment, the plasma EPA/arachidonic acid (AA) ratio increased significantly from 0.40 ± 0.2 to 1.08 ± 0.39 (P < 0.001). There were no changes in the maximum platelet aggregation (MPA) induced by adenosine diphosphate (5 and 20 µmol/L), AA (0.3 and 0.5 mg/mL), or collagen (2 and 4 µg/mL). Furthermore, no significant differences were observed in the expression of PAC-1 and CD62P on the platelet surface membranes or in the soluble P-selectin concentration. With further analysis, a significant negative correlation was found between collagen (2 µg/mL)-induced MPA and plasma EPA/AA ratio (r = -0.507, P = 0.032). The patients were then divided into 2 groups according to the median EPA/AA ratio value of 0.92. In the high EPA/AA ratio group (n = 10), collagen-induced MPA was significantly suppressed after EPA-E administration (45.3 ± 15.9 versus 39.0 ± 16.3, P = 0.033). In contrast, there were no significant changes in platelet aggregation (56.0 ± 9.8 versus 57.1 ± 11.4, P = 0.745) in the low EPA/AA ratio group (n = 8). EPA treatment had a potential to suppress collagen-induced platelet aggregation in patients with a high plasma EPA/AA ratio.