Introduction: Patent foramen ovale (PFO) closure prevents recurrent ischemic stroke in selected patients with a cryptogenic stroke. Trial results tend to be generalized to daily practice, often extending original trial inclusion criteria. This may result in unnecessary closure without benefit, but with risk of complications. We therefore introduced a standardized and structured evaluation by an interdisciplinary Heart-Stroke Team (HST). Our aim was to investigate the proportion of actual PFO closure of all referred patients with a cryptogenic stroke, after evaluation by the HST. Patients and methods: We conducted a single-center, retrospective cohort study. Patients with an assumed cryptogenic ischemic stroke or transient ischemic attack (TIA) and a PFO who were referred for PFO closure were analyzed. As part of the HST approach, all patients underwent a standardized work-up, first to demonstrate the ischemic event on neuroimaging, second to evaluate all potential causes of stroke and finally, to assess the possible relation between the PFO and stroke. Outcome was the proportion of patients treated with PFO closure after referral. Results: A total of 195 patients were included. In 124 patients (64%) PFO closure was advised. Fourty-two (22%) patients had a clear alternative cause of stroke and in 13 (7%) patients the initial stroke diagnosis could not be confirmed. Conclusion: After careful analysis of patients referred for PFO closure a relationship between the PFO and stroke could not be demonstrated in 32% of referrals, and 3% preferred best medical treatment over percutaneous closure. This stresses the need for a complete neurovascular work-up and multidisciplinary assessment.