Mesoporous silica nanoparticles are promising drug delivery agents; however, their interaction with various in vivo biological components is still under investigation. In this work, the impact of sub-50 nm diameter mesoporous silica nanoparticles on platelet function is investigated using a microfluidic platform to model blood vessel characteristics. Platelet adhesion and aggregation in the presence of mesoporous silica nanoparticles is investigated, controlling whether or not platelets are activated ahead of nanoparticle exposure. The results indicate that nanoparticles slightly compromise platelet adhesion to endothelial cells at low nanoparticle doses, but that high nanoparticle doses significantly increase the number of platelet adhesion events, leading to higher probability for uncontrolled platelet actions (e.g. clot formation in vivo). High nanoparticle doses also induced platelet aggregation. While platelet activation and aggregation occurred, in no case did nanoparticle exposure result in significant loss of platelet viability; as such, this work clearly demonstrates that aspects besides viability, such as cellular adhesion and interaction with other cell types, have to be considered in the context of nanotoxicology. This simple and highly adaptable analytical platform will be useful for further nanotoxicity studies involving other nanoparticle and cell types.