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Background: Patients have widely accepted abortion as a remedy for contraceptive failure all over the world. Esketamine is a new anesthetic, sedative, and analgesic drug. Fentanyl is an opioid receptor agonist and a commonly used sedative. It is necessary to choose appropriate sedative drugs for painless abortion., Methods: We selected 238 cases of painless induced abortion from January 2020 to January 2022. We collected surgical parameters, the performance of sedation, and postoperative scales with complications before and after the operation. SPSS 21.0 was used to analyze data., Results: Surgical indicators between intervention and control groups had no difference; the preoperative indicators including intraoperative bispectral index (BIS), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse oxygen saturation (SpO2) had no difference between the two groups. But after surgery, experiment groups had a higher value than the control group in these four indicators. The incidence of postoperative complications including nausea and vomit had no significant difference while the experiment group had a lower r -value than the control group in hypotension, bradycardia, decreased oxygen saturation, and respiratory depression. The postoperative VAS score and Ramsay score in the experimental group were lower than those in the control group., Conclusion: Since esketamine had better sedation performance, reduce the risk of cardiovascular and respiratory depression during sedation, and reduce the pain scale compared with fentanyl, we supported that propofol/esketamine is a good choice for patients receiving a painless induced abortion, and it is a sedation plan worth promoting and further analysis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Naixing Xin et al.)