BACKGROUND: The effectiveness of platelet reactivity unit (PRU)–guided individualized antiplatelet therapy for intracranial aneurysm treatment remains uncertain. METHODS: This retrospective study evaluated 1705 patients with 1883 unruptured intracranial aneurysms who received endovascular treatments at a tertiary center between March 2018 and December 2020. Patients were divided into 2 groups: a standard group (aspirin and clopidogrel without PRU) and an individualized group where antiplatelet therapy was adjusted or switched to low-dose prasugrel based on preprocedural PRU values by VerifyNow. In the individualized group, hyporesponsiveness was defined as PRU>238 or inhibition <26%, prompting transition to low-dose prasugrel, whereas hyperresponsiveness was defined as PRU<86 or inhibition >74%, leading to dose withholding. The primary outcome was thromboembolic and hemorrhagic complications within 1 month. Thromboembolic complications included intraprocedural thrombosis, transient ischemic attack, and ischemic stroke confirmed on diffusion-weighted imaging; microembolism was defined as acute diffusion-weighted imaging lesions <1 cm. Hemorrhagic complications encompassed intracranial bleeding and extracranial access site hematomas (retroperitoneal hematoma, puncture-site pseudoaneurysm). Functional outcomes were assessed using the modified Rankin Scale. Subgroup analyses were performed for complex procedures, defined as stent-assisted coiling and flow diversion. RESULTS: Average patient age was 58.0±10.8 years; 72.4% were female. The cohort included 1020 patients in the standard group and 685 in the individualized group. No significant difference in overall thromboembolic complications was observed between the standard (2.4%) and individualized groups (1.3%; P =0.127). However, individualized therapy significantly reduced thromboembolic events in complex procedures, including stent-assisted embolization and flow diversion (3.3% versus 1.0%; P =0.017; P for interaction=0.049). In the flow diverter subgroup, the incidence of microembolism was significantly lower in the individualized group (47.8% versus 26.8%; P =0.049). Hemorrhagic complication rates were similar between groups. CONCLUSIONS: Individualized antiplatelet therapy based on PRU measurements did not impact overall outcomes but reduced ischemic complications in complex endovascular treatments without increasing bleeding risks. Further validation is necessary.