Platelets are playing a crucial role in acute cardiovascular events. We investigated if physical stress activates platelets and whether this activation can be inhibited by a polyphenol-enriched diet.Blood samples were taken from a total of 103 athletes three weeks before, one day before, immediately as well as 24 hours and 72 hours after a marathon run. Participants were randomized, double-blinded and divided into two groups. One group received a polyphenol-rich beverage the other the same beverage without polyphenols. Besides analysis of platelet counts and impedance-aggregometric-measurement of platelet activity, soluble P-selectin and Endothelin-A measurements were performed.In the control group, runners showed a 2.2-fold increased platelet aggregation directly after completing a marathon and within the following three days when compared with baseline values (p<0.01). In accordance, significant increases in sP-selectin (57.52ng/ml vs. 94.86ng/ml; p<0.01) were detectable. In contrast, for the group consuming a beverage with increased polyphenol content (upper quartile of study beverage intake) we did not find any increase of platelet aggregation.Physical stress causes a significant increase in platelet activity. Our results demonstrate that a diet enriched in polyphenols is capable of preventing platelet activation. These findings might indicate a diminished cardiovascular stress-reaction following pre-exposition to polyphenol-enriched diet.