© 2017 American Heart Association, Inc. Background and Purpose - Thromboembolic complications constitute a significant source of morbidity after neurointerventional procedures. Flow diversion using the pipeline embolization device for the treatment of intracranial aneurysms necessitates the use of dual antiplatelet therapy to reduce this risk. The use of platelet function testing before pipeline embolization device placement remains controversial. Methods - A retrospective review of prospectively maintained databases at 3 academic institutions was performed from the years 2009 to 2016 to identify patients with intracranial aneurysms treated with pipeline embolization device placement. Clinical and radiographic data were analyzed with emphasis on thromboembolic complications and clopidogrel responsiveness. Results - A total of 402 patients underwent 414 pipeline embolization device procedures for the treatment of 465 intracranial aneurysms. Thromboembolic complications were encountered in 9.2% of procedures and were symptomatic in 5.6%. Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications compared with clopidogrel responders (17.4% versus 5.6%). This risk was significantly lower in nonresponders who were switched to ticagrelor when compared with patients who remained on clopidogrel (2.7% versus 24.4%). In patients who remained on clopidogrel, the rate of thromboembolic complications was significantly lower in those who received a clopidogrel boost within 24 hours pre-procedure when compared with those who did not (9.8% versus 51.9%). There was no significant difference in the rate of hemorrhagic complications between groups. Conclusions - Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications when compared with clopidogrel responders. However, this risk seems to be mitigated in nonresponders who were switched to ticagrelor or received a clopidogrel boost within 24 hours pre-procedure.