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BACKGROUND HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABAA) receptor. OBJECTIVE To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN A single-blinded, randomised, parallel-group, phase 3 trial. SETTING Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonbrain elective surgery. INTERVENTION Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg-1) or propofol (2.0 mg kg-1) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg-1 h-1, and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery. MAIN OUTCOME MEASURES Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P = 0.451) in the HSK3486 and propofol groups. CONCLUSION HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION Clinicaltrials.gov, identifier: NCT04511728.