Quantum dots (QDs) are semiconducting inorganic nanocrystals, that have garnered interest in biological and medical spheres due, to their potential benefits in biomedical imaging and drug-delivery systems. Indium phosphide QDs shelled with zinc sulphide (InP/ZnS) are viewed as more biocompatible than previous heavy metal based QDs. However, little is known about how InP/ZnS QDs affect a key blood cell, the platelet. Understanding how platelets interact with QDs is critical as unwanted activation can lead to pathological thrombus formation. Herein, we demonstrate PEGylation of InP/ZnS QDs coated with lipoic acid (QD-LA) or coated with penicillamine (QD-Pen) surface ligands induced markedly less platelet aggregation, platelet-QD interactions, integrin activation, alpha granule secretion and restored platelet spreading in washed platelets in comparison to their non-PEGylated counterparts. Furthermore, in whole blood, PEGylation of QDs reduced the number of QDs in the thrombus, thereby helping to minimise the chance of dysfunctional thrombus formation. Overall, we show that QD PEGylation is important to help prevent QD mediated platelet activation. In combination with the most biocompatible coating, PEGylation markedly reduced platelet activation, widening the concentrations at which QDs were viable for development as potential drug delivery or imaging agents.