Common complications during MitraClip procedure are bleeding and ischemic events. The right strategy of platelet inhibition is unknown and challenging, as there are substantial interindividual response-variabilities to antiplatelet drugs and additionally, many MitraClip patients are on permanent oral anticoagulation because of atrial fibrillation. We aimed to investigate the incidence of (i) high- and low on-treatment platelet reactivity (HTPR, LTPR) to antiplatelet medication and (ii) clinical complications in MitraClip patients.In an observational single-center cohort study we investigated 73 patients who underwent MitraClip implantation. Clopidogrel effects were measured using the vasodilator-stimulated protein phosphorylation (VASP) assay, aspirin effects by light-transmission aggregometry (LTA). Clinical complications were investigated during six-month follow-up.HTPR to clopidogrel was observed in 44 patients, LTPR to clopidogrel in 6 patients. 16 patients had HTPR to aspirin. Major complications occurred in 12 patients, overall bleeding complications in 27 patients, overall ischemic events in two patients. The incidence of HTPR/LTPR did not differ between patients with- vs. without clinical complications. Bleeding complications were not more frequent in patients with additional oral anticoagulation.In this study, the incidence of HTPR to clopidogrel was very high (60% of patients). Despite these insufficient clopidogrel antiplatelet effects, ischemic events were rare and bleeding complications more frequent. Additionally, many patients undergoing MitraClip procedure were on permanent oral anticoagulation because of atrial fibrillation. The optimal antithrombotic regiment should be investigated in large scale clinical trials under consideration of the high incidence of HTPR to clopidogrel medication in MitraClip patients.