We propose a mechanism of how stroke may be caused by thrombus aspiration during primary percutaneous coronary intervention (PPCI), and how it may be technique‐dependent.Two recent meta‐analyses report increased risk of stroke in patients undergoing routine thrombus aspiration during STEMI and the value of this technique has been controversial. The mechanism of stroke has not been fully explained.This case demonstrates 2 mechanisms by which aspiration might cause thrombus embolization.We recommend that if thrombus aspiration is performed during PPCI for STEMI, it should be done selectively and carefully. It is prudent to make sure the guide catheter tip is not free in the aorta when the aspiration catheter is withdrawn, to maintain suction on the aspiration catheter as it is withdrawn (particularly if the aspiration port seems to be obstructed), and to aspirate the guide catheter after the aspiration catheter is removed to capture any fragments of thrombus that remain in the guide catheter. © 2016 Wiley Periodicals, Inc.