Background <p>The oculocardiac reflex (OCR) is the most common complication in pediatric strabismus surgery, and its main clinical manifestation is bradycardia. Esketamine can activate the sympathetic nervous system, leading to an indirect cardiovascular stimulation effect, which results in increased blood pressure and a faster heart rate. The aim of this study is to explore whether a sub-anesthetic dose of esketamine can effectively inhibit the oculocardiac reflex during strabismus surgery.</p> Method <p>This prospective, single-center, randomized, double-blinded trial will enroll 204 pediatric patients undergoing strabismus surgery. Participants will be randomly assigned to esketamine (group S) and control groups (group C) in a 1:1 ratio. Esketamine (0.2&#xa0;mg/kg) or an equal volume of normal saline will be administered after anesthesia induction. The OCR is defined as a sudden decrease in heart rate (HR) of 20% from baseline, and severe OCR will be defined as profound bradycardia (HR &lt; 50 beats per minute). The primary outcome is the incidence of overall OCR during surgery. Secondary outcomes include severe OCR during all stages, the incidence of OCR at various stages of surgery, postoperative agitation, postoperative nausea and vomiting, procedure suspension frequency, and atropine administration requirements.</p> Discussion <p>The purpose of this study is to explore whether the administration of a sub-anesthetic dose of esketamine in pediatric strabismus surgery can reduce the incidence of OCR during surgery. The findings of this study may offer a new perspective and direct clinical evidence for the prevention and treatment of OCR during the perioperative period.</p> <p>Trial registration.</p> <p>Chinese Clinical Trial Registry (ChiCTR2400094053). Registered on 16 December 2024, <a href="http://www.chictr.org.cn">www.chictr.org.cn</a>. Prospectively registered.</p>