Background: Observational studies have favored percutaneous patent foramen ovale (PFO) closure over medical treatment for the reduction of recurrent stroke, as randomized trials have failed to demonstrate the significant superiority of percutaneous PFO closure. A few long- term studies are available on post-PFO closure outcome. This study reports long- and short- term clinical outcomes after percutaneous PFO closure. Methods: Between January 1998 and January 2015, we enrolled 51 (32 men [62.7%] and 19 [37.3%] women) consecutive eligible patients with cerebrovascular events or peripheral embolism, presumably related to PFOs, who underwent percutaneous PFO closure in our center. All the patients’ documents and clinical data were assessed. Of the entire study population, telephone contacts were applied in 47 cases. The mean follow-up time was 46.51 ± 43.43 months. The main criterion for closure was patients with at least 1 cryptogenic stroke or peripheral embolism associated with PFOs. Results: Percutaneous PFO closure was successfully performed in 51 patients. No cardiovascular or cerebrovascular deaths occurred. The mean follow-up time was 46.51 ± 43.43 months. Long-term device-related complications were cerebrovascular accidents in 3 (5.88%) patients (2, 3, and 4 y after the procedure) and open heart surgery in 1 (1.96%). The short- term complications were atrial fibrillation in 1 (1.96%) patient, air embolism in 2 (3.92%), hematoma in 2 (3.92%), and tamponade in 1 (1.96%). Conclusions: Percutaneous PFO closure was associated with a very low risk of recurrent stroke. We observed no cardiovascular or cerebrovascular mortality; however, there were a few short- and long-term device-related complications. Thus, percutaneous PFO closure is a safe treatment even in the long term. (Iranian Heart Journal 2017; 17(4): 6-16)