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Variable response to clopidogrel can impact perioperative risk in elective endovascular intracranial aneurysm treatment. The present study aims to determine the efficacy of a two-test protocol in reaching in-range preoperative P2Y12 reaction units (PRU) of 60–240 and the rate of postoperative conversion to hyper-response.A 17-day two-test protocol (with tests on days 10 and 17) for patients starting clopidogrel in anticipation of elective endovascular intracranial aneurysm treatment was introduced in February 2013 at our institution. Records for patients started on this protocol through December 2014 were reviewed for preoperative and postoperative PRUs, patient and procedural data, and thromboembolic and hemorrhagic events within 30 days. Logistic regression analyses were performed to identify predictors of postoperative hyper-response (p<0.05 considered significant).103 patients (80 women) of mean age 57 years were included. 74 patients (71.8%) were in range at the first test and 92 patients (89.3%) were in range at the second test. A postoperative test was performed in 82 patients (79.6%) at a median of 9 days. 51 patients (62.2%) converted into hyper-responders. There were five non-disabling strokes and one intracranial hemorrhage within 30 days. There were no major strokes (modified Rankin Scale score >2) or deaths. There was no association between out-of-range PRU and thromboembolic or hemorrhagic neurological complications.The protocol achieves in-range preoperative PRU by the second test in almost nine of 10 patients. Nearly two-thirds of patients exhibited postoperative hyper-response to clopidogrel. Out-of-range PRU was not associated with thromboembolic or hemorrhagic neurological complications in this cohort of patients with actively managed P2Y12 inhibition.