Several uncontrolled studies suggested a relationship between patent foramen ovale (PFO) and stroke. But recent data indicate that previous studies may overestimate the association between PFO and stroke. First, among patients who have had a cryptogenic stroke under treatment (with either warfarin or aspirin), the main data from the French PFO/atrial septal aneurysm (ASA) and PICSS (Patent Foramen Ovale in Cryptogenic Stroke Study), analyzed separately and in combination, indicate that PFO alone does not announce a significantly increased risk of recurrent stroke or death. But a small increase or decrease in risk cannot be excluded by this meta-analysis. Second, the data concerning the association between PFO and ASA are not clear and variable: the French PFO/ASA study found a significantly increased risk of recurrent stroke in patients with cryptogenic stroke and an association between PFO and ASA when treated medically. In contrast, PICSS found no association between the combined PFO-ASA with stroke or death, but the two populations had meaningful differences. Patients in the PICSS were much older than those in the French PFO/ASA study and had more risk factors for stroke, such as hypertension, diabetes, and history of prior stroke. Third, there were inadequate data to conclude about ASA alone. Possible practice recommendations could come from this meta-analysis: the evidence indicates that the risk of recurrent stroke or death is not different for patients with a PFO who underwent cryptogenic stroke compared to patients without a PFO who underwent a cryptogenic stroke under treatment with either aspirin or warfarin. But aspirin is more preferable (300 mg/d). However, it seems that the association between PFO and ASA confers an increased risk of recurrent stroke in medically treated patients who are less than 55 years of age. This subgroup of younger stroke patients may benefit from other treatments, such as the percutaneous closure of PFO or mini-invasive surgery to a lesser extent, but their efficacy and safety are not yet assessed by large randomized trials. However, we must also keep in mind that some stroke patients with PFO are psychologically attached to their PFO and prefer to close it.