OBJECTIVE: To compare the safety and efficacy of dexmedetomidine and remifentanil with sufentanil-based general anesthesia for the transthoracic device closure of ventricular septal defects (VSDs) in pediatric patients. METHODS: A retrospective analysis was performed on 60 children undergoing the transthoracic device closure of VSDs from January 2019 to June 2020. The patients were divided into two groups based on different anesthesia strategies, including 30 cases in group R (dexmedetomidine- and remifentanil-based general anesthesia) and 30 cases in group S (sufentanil-based general anesthesia). RESULTS: There was no significant difference in preoperative clinical information, hemodynamics before induction and after extubation, postoperative pain scores, or length of hospital stay between the two groups. However, the hemodynamic data of group R were significantly lower than those of group S at the time points of anesthesia induction, skin incision, thoracotomy, incision closure, and extubation. The amount of intravenous patient-controlled analgesia (PCA), the duration of mechanical ventilation, and the length of the intensive care unit (ICU) stay in group R were significantly less than those in group S. CONCLUSION: Dexmedetomidine combined with remifentanil-based general anesthesia for the transthoracic device closure of VSDs in pediatric patients is safe and effective.