Platelet P-selectin and activated glycoprotein IIb-IIIa (GPIIb-IIIa) are markers of platelet activation and mediates platelet aggregation. Prasugrel (Pras) 5mg may be used in very elderly (VE) acute coronary syndrome (ACS) patients undergoing PCI, but its effect on platelet P-selectin and activated GPIIb-IIIa in those patients is not known. Stable ACS patients, VE (78±5years, n=23) and non-elderly (NE) (55±5years, n=22) were randomized to Pras (5 or 10mg) or clopidogrel (Clop) 75mg during three 12-day periods. Platelet activation markers were measured by flow cytometry on unstimulated or stimulated (adenosine diphosphate (ADP) 20μM) platelets, before and after each dosing period. At baseline there was no difference in platelet activation markers, either unstimulated or ADP-stimulated, between NE and VE. Pras 5mg reduced both ADP-stimulated platelet P-selectin and activated GPIIb-IIIa in VE (p<0.01 for both analyses) and NE (p<0.001 and p<0.05, respectively). Clop 75mg had a similar effect as Pras 5mg but did not significantly reduce activated GPIIb-IIIa in VE. Prasugrel 10mg resulted in decreased platelet activation in both age groups compared to Clop 75mg (p<0.01). In VE and NE-patients, Pras 5mg inhibited platelet P-selectin expression similar to Clop 75mg and Pras 10mg. Prasugrel 10mg inhibited platelet P-selectin expression better than Clop 75mg. Prasugrel 10mg and 5mg, but not Clop 75mg, significantly inhibited activated GPIIb-IIIa in VE. This platelet reactivity data support the use of Pras 5mg for VE patients.