To find the right sedation technique for different types of treatment methods and the right amount of sedatives so the chances of side effects happening can be reduced. This was a retrospective cohort analysis conducted on prospectively collected data. Patients who underwent esophagogastroduodenoscopy only (E group) were sub-divided into two subgroups: (a) Those who received 0.5 mg/kg of propofol (E-a), (b) Those who received 0.025 mg/kg of midazolam and 0.5 mg/kg of propofol (E-b). Patients who underwent esophagogastroduodenoscopy with colonoscopy (EC group) were also sub-divided into three subgroups: (a) Those who received 0.5 mg/kg of propofol (EC-a), (b) Those who received 0.025 mg/kg of midazolam and 0.5 mg/kg of propofol (EC-b), (c) Those who received 25 mg (12.5 mg if body weight < 50 kg or age > 70) of meperidine and 0.025 mg/kg of midazolam along with 0.5 mg/kg of propofol (EC-c). When the level of target was not reached, 10-20 mg of propofol was additionally injected. Sedation efficacy and safety were then compared among groups. E-b and EC-b decreased the overall amount of propofol and reduced side effect of temporary hypoxemia compared to E-a and EC-a. EC-b shortened patient recovery time compared to EC-c and reduced paradoxical reaction. In terms of the patient satisfaction and patient cooperation by endoscopists, there were no significant differences between EC-b and EC-c. Concomitant use of low dosages of both propofol and midazolam is found to be useful and safe when endoscopy needs to be performed.