Background: Recent case control studies suggest that patients with subacute stent thrombosis (SAT) have increased platelet reactivity. However, SAT often presents as acute myocardial infarction (AMI), which is also associated with augmented platelet activation. We therefore compared platelet reactivity in patients with SAT and patients with AMI unrelated to stenting. Methods: We identified 20 patients with SAT, 20 patients with ST-elevation AMI who underwent primary percutaneous coronary intervention (PCI), and 20 patients who underwent stenting without SAT occurrence (stable control group). Platelet function was measured ≥3 days after PCI in the SAT (repeat procedure) and AMI groups and ≥3 months after stenting in the stable group. All patients received aspirin and clopidogrel. Platelet reactivity was evaluated by aggregation in response to 5 and 20 μmol/L of adenosine diphosphate and 1.5 mmol/L arachidonic acid, and by flow cytomeric determination of P-selectin and glycoprotein IIb/IIIa activation. Results: Clinical characteristics were similar among the groups. Platelet testing was performed 4.9 ± 1.7, 3.1 ± 0.3, and 108 ± 22 days after PCI in the SAT, AMI, and stable groups, respectively. The SAT group had higher platelet aggregation and activation markers than the stable group. However, platelet aggregation and activation was very similar in the SAT and AMI groups. Conclusions: Patients with SAT have increased platelet reactivity, compared with patients who do not develop SAT following stenting. However, the augmented platelet reactivity does not appear to differ from patients with AMI unrelated to stenting. This study highlights the need for large prospective studies to determine whether platelet hyperreactivity increases the risk of SAT.