Closure of a patent foramen ovale (PFO) in patients after cryptogenic/cardioembolic stroke is recommended by current guidelines for patients who are 16–60 years of age with a high-risk PFO (class of recommendation A, level of evidence I). The use of double-disk occlusion devices followed by antiplatelet therapy is recommended. The procedure of interventional PFO closure compared with other interventions in cardiology is rather easy to learn. However, it should be performed carefully to avoid postinterventional complications. The number needed to treat (NNT) to avoid one stroke in 5 years in the RESPECT trial was 42, in the CLOSE trial even lower with 20. In the REDUCE trial, the NNT was 28 at 2 years. This can be reduced by longer follow-up, e.g., at 10 years the NNT is 18. While other conditions such as migraine are currently under investigation with respect to the impact of PFO closure, sufficiently powered trials are lacking so that closure in diseases other than stroke should always be individualized.