Background and Aim: Automobile driving is prohibited after midazolam sedation because of the slow recovery of psychomotor function. This study prospectively assessed the safety of low-dose propofol sedation (study 1) and compared driving ability following propofol and midazolam sedation (study 2). Methods: Study 1: We prospectively investigated bolus injection of a low-dose of propofol (40–80 mg for <70 years and 30 mg for ≥70 years) for diagnostic esophagogastroduodenoscopy (EGD). Respiratory depression, time to full recovery, and overall patient satisfaction were evaluated and blood concentrations of propofol were measured. Study 2: A subset of subjects undergoing diagnostic EGD were randomized to receive 40 mg of propofol (n = 30), 4 mg of midazolam (n = 30) or no sedation controls (n = 20), and the residual effects of each drug were tested using a driving simulator. The primary outcome measure was driving ability. The second outcome measures were overall patient satisfaction and complications. Results: Study 1: Only 1.1% of 12,031 healthy subjects developed transient oxygen desaturation. Full recovery was present in 97.5% 30 min after the procedure; 99.8% were willing to repeat the same procedure. The blood levels of propofol (40–80 mg) at 60 min were <100 ng/ml. Study 2: Driving ability recovered to the basal level within 60 min of propofol administration but not with 120 min with midazolam. There were no complications; overall patient satisfaction was similar between propofol and midazolam (8.9 vs. 8.5, p = 0.34). Conclusion: Low-dose propofol sedation was safe and recovery including driving ability was with 60 min.

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