Clinical studies have pointed out a possible interaction between aspirin and omeprazole. In a recent study in aspirin treated patients, proton pump inhibitors (PPIs) were linked to an increased risk of adverse cardiovascular events. A recent proteomic study has described the presence of proton pumps in human platelets. This work looked into the modulation of aspirin antiplatelet effect by omeprazole and the effect of omeprazole alone on platelet activity. Incubation of omeprazole with aspirin, compared to aspirin alone, showed no significant difference on thromboxane A2 generation (p>0.05). However, it significantly (p>0.05) decreased platelet aggregation and granular secretion. Incubation of omeprazole in plasma caused a significant decrease of TxA2 generation and platelet granular secretion compared to control conditions, but aggregation remained unchanged. Omeprazole may enhance the antiplatelet effect of aspirin by another mechanism than COX-1 inhibition. The hypothesis about proton pumps role in the growth and stabilisation of the platelet plug is a given, but further studies are needed.