Aspirin ingestion sensitizes platelets to cyclophilin D inhibition in human subjects. Platelets from healthy volunteers were examined before and after 7 days of aspirin ingestion. Washed platelets were activated with thrombin (0.1 U/mL) and collagen (5 µg/mL) and GSAO⁺/P-selectin⁺ necrotic platelets measured by flow cytometry (A) and procoagulant potential assessed using the Calibrated Automated Thrombogram (B). Aspirin ingestion resulted in no change in the GSAO⁺/P-selectin⁺ necrotic or procoagulant potential of activated platelets. CysA treatment of preaspirin platelets resulted in a decrease in GSAO⁺/P-selectin⁺ necrotic platelets (n = 5;* P < .05) and procoagulant function (n = 5; **P < .01), and this effect was more pronounced in the postaspirin platelets (n = 5; *P < .05).