Stroke is a rare but possible complication after atrial fibrillation (AF) ablation. However, its etiopathogenesis is far from being completely characterized. Here we report a case of stroke, with recurrent peripheral embolism after AF ablation procedure. In our patient, an in situ femoral vein thrombosis and iatrogenic atrial septal defect were simultaneously detected. A comprehensive review of multiple pathophysiological mechanisms of stroke in this context is provided. The case underlines the importance of a global evaluation of patients undergoing AF ablation.