A 65-year-old female presented with severe left cervical internal carotid artery stenosis manifesting as repeated transient ischemic attacks(TIAs) consisting of right hemiparesis and motor aphasia. Carotid artery stenting (CAS) under distal protection was performed to prevent further ischemic events. This procedure was uneventful. However, the patient exhibited progressive right hemiparesis and motor aphasia three hours after CAS. Emergent angiography revealed carotid artery occlusion due to acute carotid in-stent thrombosis (ACIST). Mechanical thrombectomy was performed. The carotid artery was recanalized with small residual thrombus. The neurological deficits partial disappeared after mechanical thrombectomy following catheter directed thrombolysis combined with a continuous intra-arterial infusion of low-dose tirofiban for ACIST. Follow-up angiography 9 months after stenting showed lessens restenosis and no in-stent thrombosis. Carotid thrombosis after CAS can be resolved by mechanical thrombectomy combined with in-stent catheter directed intra-arterial thrombolysis with a continuous infusion of low-dose tirofiban for more than 24hr and subsequent treatment with antithrombotic agents. This management is a feasible solution to ACIST.