ObjectiveTo compare effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on platelet function in patients undergoing cardiac rehabilitation, as hyper-reactive platelets are involved in atherogenesis and atherothrombosis.MethodsIn this single-centre parallel group randomised controlled trial, male patients after an acute coronary syndrome under dual antiplatelet therapy performed MICT or HIIT+MICT for 12 weeks. Main outcome was platelet reactivity measured by the half-maximal concentration (EC₅₀) of platelet agonist thrombin receptor-activating peptide-6 (TRAP-6) in terms of P-selectin expression. EC₅₀ was determined at baseline, after 6 and 12 weeks, each time at physical rest and on exertion.Results82 patients were randomised to MICT or HIIT+MICT. Mean (95% CI) baseline EC₅₀values at physical rest were 6.7 µM (6.3 µM to 7.0 µM) TRAP-6. After 6/12 weeks, 36/33 MICT and 34/28 HIIT+MICT patients were examined. HIIT+MICT patients had 0.9 µM (0.4 µM to 1.4 µM)/0.5 µM (−0.1 µM to 1.0 µM) higher EC₅₀values than MICT ones, and the propensity of their platelets to form aggregates with monocytes was significantly lower after 12 weeks. Short-term strenuous physical exertion was generally associated with platelet activation and an EC₅₀reduction of 0.7 µM (0.6 µM to 0.8 µM). HIIT+MICT patients tended to be fitter after 12 weeks. No serious harms were observed.ConclusionsIncluding HIIT in cardiac rehabilitation seems to confer additional benefits compared with MICT alone, which should be confirmed in clinical trials with hard endpoints. Exertion-induced platelet activation and hyper-reactivity occur despite dual antiplatelet therapy.Trial registration numberNCT02930330; Results.