Stroke is a serious complication after acute myocardial infarction (AMI) and is associated with an increased risk of death. Though the pathophysiological mechanisms are not exactly known, increased inflammation and platelet reactivity could play an important role in the occurrence of stroke during AMI. We aimed to investigate the relationship between both mean platelet volume (MPV), a parameter of platelet function, and C-reactive protein (CRP) and the occurrence of in-hospital ischemic stroke (IHS) after AMI. Data were obtained from a French regional survey for AMI that included 5976 patients admitted to an intensive care unit (ICU) between 2001 and 2010. Patients were divided into two groups according to the occurrence of IHS. MPV, platelet count (PC), and CRP were routinely measured at admission to the ICU; 99 (1.6%) IHSs were recorded during hospitalization after admission for AMI. In multivariate analysis, IHS was independently associated with a history of stroke (OR: 1.99%, CI: 1.1–3.49, p = 0.01), impaired left ventricular ejection fraction 10 mg/l (OR: 2.19, 95% CI: 1.44–3.33, p