Essentials Pharmacodynamic response to antiplatelet medication is heterogeneous. Platelet reactivity to dual antiplatelet therapy was analyzed by three platelet function assays. The prevalence of high and low platelet reactivity differed significantly between assays. Future trials are needed to determine the best assay to analyze platelet function.Background High on-treatment platelet reactivity (HTPR) to antiplatelet medication leads to ischemic events, whereas low on-treatment platelet reactivity (LTPR) increases bleeding risk. However, various trials have failed to demonstrate superiority of tailored antiplatelet regimens (ARCTIC, ANTARCTIC, Trigger-PCI, and GRAVITAS). TROPICAL-ACS was the first study that demonstrated the benefit of tailoring antiplatelet medication according to platelet function analysis. A potential reason may be that different platelet function assays were used in these trials. Objectives To evaluate whether the results of platelet function tests are comparable. Patients/Methods We tested three commonly used assays - light transmission aggregometry (LTA), (Multiplate impedance aggregometry [MP]), and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) - in 23 patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Results With LTA, HTPR occurred in 57% of patients; with VASP, it occurred in 43% of patients; and with MP, it occurred in 13% of patients. According to LTA, only 35% of patients were in the therapeutic window; according to VASP, 57% of patients were in the therapeutic window; and according to MP, 48% of patients were in the therapeutic window. With LTA, LTPR occurred in 9% of patients; with VASP, it occurred in 0% of patients; and with MP, it occurred in 39% of patients. Therefore, the prevalences of HTPR and LTPR differed significantly between assays. Remarkably, in 17% of patients, one assay showed HTPR whereas another showed LTPR. Conclusions The results of different platelet function assays differ substantially. Up to now, only TROPICAL-ACS had demonstrated a benefit of tailoring antiplatelet medication according to platelet function analysis. Future trials are needed to evaluate whether the platelet function assay used in TROPICAL-ACS is the 'correct' one and revives platelet function testing.