Recurrent sequential mechanical thrombectomy for cryptogenic large vessel occlusion (LVO) can lead to excellent clinical outcome. A 68-year-old right-handed male presented with an acute proximal right middle cerebral artery (MCA) ischemic syndrome and underwent successful revascularization by mechanical thrombectomy with normal functional recovery. He was treated with dual antiplatelet therapy for 2 months following discharge, however later discontinued clopidogrel due to side effects. He then developed a recurrent, contralateral MCA occlusion 16 months later and once again received emergent endovascular reperfusion therapy with excellent neurological outcome. He has remained on off-label empiric oral anticoagulation since and has not had recurrent stroke nor evidence of cerebral ischemia. Favorable clinical outcomes can be achieved in patients despite recurrent LVO who underwent emergent mechanical thrombectomy. Optimal antithrombotic secondary stroke prevention strategies following embolic stroke of unknown source remains uncertain as recent evidence does not support rivaroxaban or dabigatran over aspirin. The benefit of apixaban over aspirin for the prevention of recurrent cerebral ischemia is under current investigation.