Transcatheter closure of septal defects has become a widely used alternative to surgery or life-long anticoagulant therapy especially in patients with atrial septal defects (ASD) and patent foramen ovale (PFO). Post-procedural complications include thrombus formation on the occluder in about 0-10% of all cases. Therefore antithrombotic prophylaxis after device implantation is believed to be necessary, but still is variable and remains controversial. To date no randomized studies have been published to assess the optimal anticoagulation strategy. Thus, therapy is based on empirical data, local experience and case reports from the literature. The present review tries to give an overview on most of these mainly retrospective single center studies and summarizes their results. Factors influencing the rate of thrombus formation may be device type, existence of thrombophilic disorders and prophylactic medication. Thrombus formation has been described for each of the existing occluder types without a significant difference between the devices. For antithrombotic prophylaxis, most centers at present use either acetyl salicylic acid alone (ASA; 81 to 325 mg) for 6 months or a combination of ASA and clopidogrel (75 mg) for 6 to 8 weeks followed by ASA for additional 4 to 8 months. Inherited thrombophilic disorders should be excluded before device implantation in order to adapt antithrombotic prophylaxis. Follow-up examinations after device implantation should be performed using TEE within the first 4 weeks after implantation. Thus, thrombi may be recognized early enough to extend the antithrombotic regimen in order to avoid surgical device explantation.