Dual antiplatelet therapy is established for prevention of stent thrombosis in cardiac patients, and widely utilized in neurointerventional stent cases. Aspirin and clopidogrel are typically synergistic. We present a case of clopidogrel resistance due to genetic polymorphism resulting in acute stent thrombosis during elective stent-assisted coiling, with novel use of prasugrel as an alternative platelet inhibitor in the neurovascular setting.