BACKGROUND: Clopidogrel is routinely used to decrease ischemic complications during neurointerventional procedures. However, the efficacy may be limited by antiplatelet resistance. PURPOSE: Our aim was to analyze the efficacy of prasugrel compared with clopidogrel in the cerebrovascular field. DATA SOURCES: A systematic search of 2 large databases was performed for studies published from 2000 to 2018. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting treatment-related outcomes of patients undergoing neurointerventional procedures under prasugrel, and studies comparing prasugrel and clopidogrel. DATA ANALYSIS: Random-effects meta-analysis was used to pool the overall rate of complications, ischemic and hemorrhagic events, and influence of the dose of prasugrel. DATA SYNTHESIS: In the 7 included studies, 682 and 672 unruptured intracranial aneurysms were treated under prasugrel (cases) and clopidogrel (controls), respectively. Low-dose (20 mg/5 mg; loading and maintenance doses) prasugrel compared with the standard dose of clopidogrel (300 mg/75 mg) showed a significant reduction in the complication rate (OR = 0.36; 95% CI, 0.17–74, P = .006; I2 = 0%). Overall, the ischemic complication rate was significantly higher in the clopidogrel group (40/672 = 6%; 95% CI, 3%–13%; I2 = 83% versus 16/682 = 2%; 95% CI, 1%–5%; I2 = 73%; P = .03). Low and high loading doses of prasugrel were associated with 0.6% (5/535; 95% CI, 0.1%–1.6%; I2 = 0%) and 9.3% (13/147; 95% CI, 0.2%–18%; I2 = 60%) intraperiprocedural hemorrhages, respectively ( P = .001), whereas low and high maintenance doses of prasugrel were associated with 0% (0/433) and 0.9% (2/249; 95% CI, 0.3%–2%; I2 = 0%) delayed hemorrhagic events, respectively ( P = .001). LIMITATIONS: Retrospective series and heterogeneous endovascular treatments were limitations. CONCLUSIONS: In our study, low-dose prasugrel compared with clopidogrel premedication was associated with an effective reduction of the ischemic events with an acceptable rate of hemorrhagic complications.