This study evaluated platelet function for an extended period of time in patients with a HeartMate II continuous-flow left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) with light transmission aggregometry and investigated the potential role of this test in clinical management. Twenty-four patients were studied prospectively after implantation. Mean duration of support was 8.5 months. Platelet functions were assessed with light transmission aggregometry induced by thrombin receptor agonist peptide, ristocetin, or arachidonic acid. All patients received an aspirin regimen that was progressively increased until arachidonic acid-triggered platelet aggregation dropped lower than 20%. Plasma levels of von Willebrand factor were also determined when ristocetin-induced platelet agglutination was impaired. Intensity of platelet aggregation with thrombin receptor agonist peptide was little changed in patients with a HeartMate II relative to control subjects. Aspirin dose greater than 160 mg/d was progressively required in 46% of patients. Ristocetin-induced platelet agglutination was impaired in 4 patients in association with a lack of high molecular weight von Willebrand factor multimers. Three patients had thromboembolic events (12.5%) and 8 (33%) suffered from major bleeding complications. High platelet reactivity during treatment with aspirin is common in patients with a HeartMate II. Moreover, light transmission aggregometry may detect impaired ristocetin-induced platelet agglutination, enabling dosage of aspirin to be adjusted. Our strategy showed no major improvements in terms of thrombosis rate when compared with published data, although bleeding frequency was somewhat reduced. Benefits of light transmission aggregometry testing need to be assessed in a larger randomized study with a longer follow-up.