Neutrophil elastase (NE) upregulates the fibrinogen binding activity of the platelet integrin αIIbβ3through proteolysis of the αIIbsubunit. This cleavage allows a strong potentiation of platelet aggregation induced by low concentrations of cathepsin G (CG), another neutrophil serine proteinase. During this activation process, we observed a strong fibrinogen binding and aggregation‐dependent phosphatidylinositol 3,4‐bis‐phosphate (PtdIns(3,4)P2) accumulation. PtdIns(3,4)P2has been suggested to play a role in the stabilization of platelet aggregation, possibly through the control of a maintained αIIbβ3integrin activation. Here we show that inhibition of phosphoinositide 3‐kinase (PI 3‐K) by very low concentrations of wortmannin or LY294002 transformed the irreversible platelet aggregation induced by a combination of NE and low concentrations of CG into a reversible aggregation. However, although inhibition of PI 3‐K was very efficient in inducing platelet disaggregation, it did not modify the level of αIIbβ3activation as assessed by binding of an activation‐dependent antibody. These results indicate that PI 3‐K activity can control the irreversibility of platelet aggregation even under conditions where αIIbβ3integrin remains activated.