〔Abstract〕 Objective To investigate the efficacy of propofol combined with dexmedetomidine in transesophageal echocardiography (TEE) guided percutaneous atrial septal defect (ASD) closure. Methods A total of 90 patients with ASD admitted to Quanzhou First Hospital affiliated to Fujian Medical University from March 2018 to February 2021 were selected and divided into observation group and control group by simple randomization method, with 45 patients in each group. The control group was given endotracheal intubation and general anesthesia, and the observation group was given propofol combined with dexmedetomidine. The quality of sedation, recovery, bispectral index (BIS), heart rate (HR), mean arterial pressure (MAP), oxidative stress and incidence of adverse reactions were compared between two groups. Results There was no significant difference in awake sedation score (OAA/S) between the two groups (P > 0.05). The time to wake up in the observation group was shorter than that in the control group, and the awake score was higher than that in the control group, with statistical significance (P < 0.05). There was no significant difference in BIS value between two groups at the same time point (P > 0.05). At the end of operation (T4), HR and MAP in the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). One day after surgery, superoxide dismutase(SOD) level in the observation group was higher than that of the control group, monochrome display adapter(MDA) level was lower than that of the control group, the difference was statistically significant (P < 0.05). The incidence of sore throat in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Propofol combined with dexmedetomidine can achieve sedation effect similar to that of general anesthesia in TEE-guided percutaneous chamber closure, which is helpful to inhibit oxidative stress, maintain hemodynamic stability, improve the quality of recovery, and reduce adverse reactions.