Provided herein are methods for protecting distal vessels from emboli during aspiration, the method comprising delivery and deployment of an emboli protection device which is advanced and placed distally relative to the clot burden and thus deep in the neurovascular bed until the device, once deployed, fully opposes a vessel wall creating a circumferential seal across the vessel. The methods utilizing the emboli protection device protect distal vasculature from vulnerable clot emboli which become dislodged during clot removal and/or aspiration and trapped in the emboli protection device.