Background <p>Most patients undergoing carotid endarterectomy (CEA) are complicated with coronary artery disease and at high risk for cardiovascular events. This study aims to regulate cerebral blood flow by adjusting the level of partial pressure of end-tidal carbon dioxide (P_ETCO₂) to reduce intraoperative blood pressure fluctuations and improve cardiac function.</p> Methods <p>In this randomized controlled trial, we randomly assigned 44 patients to receive a P_ETCO₂ target of 45-50mmHg during carotid artery occlusion and 30-35mmHg after opening, and 44 patients to receive a P_ETCO₂ target of 35-45mmHg throughout the operation. The primary outcome was E/e’ (the peak velocity of early filling/the early diastolic mitral annular velocity). Secondary outcomes included global longitudinal strain (GLS) of the left ventricular myocardium, dMAP (the change rate of mean arterial pressure relative to the baseline level) and the incidence of postoperative complications.</p> Results <p>Sixty nine&#xa0;patients were finally included, 34 patients in the control group and 35 patients in the intervention group. No significant differences were found between the groups for E/e’ (<i>P</i> = 0.614), GLS (<i>P</i> = 0.231), or the incidence of postoperative complications (<i>P</i> &gt; 0.05). The dMAP of patients during carotid artery occlusion in the intervention group was lower than that in the control group (9.1% ±10.5% vs 14.3% ±9.2%, <i>P</i> &lt; 0.05).</p> Conclusions <p>P_ETCO₂ did not have a significant impact on cardiac function.</p> Trial registration <p>This trial was registered on the Chinese Clinical Trial Registry (<a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>,&#xa0;ChiCTR2100049772; August 9, 2021).</p>