Background: The same‑day bidirectional endoscopy (BDE) under anesthesia is commonly performed for its efficacy. Until now, the optimal regimen of sedation for same‑day BDE is still inconclusive. Aim: The aim of this study is to investigate the relationship between the effect‑site concentration at loss of consciousness (CeLOC) and maximal maintained Ce (CeM) in patients undergoing sole propofol sedation with the targeted‑controlled infusion (TCI) pump and to explore the potential factors for extra fentanyl administration for same‑day BDE to improve the quality of anesthesia. Methods: After excluding the patients with different anesthesiologists/endoscopists and esophagogastroduodenoscopy before colonoscopy, a total of 183 patients receiving BDE with the American Society of Anesthesiologists I to III were enrolled. Anesthesia with TCI of propofol ranged from 2.5 to 5.0 g/mL was administrated and propofol was increased in steps of 0.5 g/mL when inadequate or too deep sedation during the procedure. If the sedation level failed to meet satisfaction after two times of Ce increments or CeM achieve 5.0 g/mL, bolus of fentanyl (25 g) would be administered. The age, height, weight, gender, CeLOC, CeM, awake Ce, anesthesia time, examination time, frequency of TCI adjustments, total consumption of propofol or fentanyl, incidence of patient movements affecting the procedure, and use of ephedrine or atropine were retrieved from anesthetic charts and electronic medical record was recorded and the factors affecting the extra bolus of fentanyl or CeM were calculated. Results: One hundred and fifty‑seven patients underwent procedures with only propofol sedation and 26 patients with additional fentanyl bolus 25 g. There were three patients with hypotension, bradycardia, and transient hypoxemia in only propofol sedation, respectively. The incidence of patient movements affecting the procedure was 36.6% (67/183), 41 patients completed the procedure after increasing propofol Ce, and 26 patients required an extra bolus of fentanyl. After linear regression, the optimal formula was CeM = 1.9 – (0.006 × age) + 0.658 × CeLOC. After controlling for confounding covariates, only CeLOC was the most informative covariate for the demand for fentanyl. Finally, we simplified the formula as propofol CeM = CeLOC + 0.7 μg/mL to avoid patient movements affecting the procedure and adverse effects. Conclusion: We showed that the age and CeLOC were associated with CeM and only higher CeLOC (>4.5 μg/mL) was the only contributing factor for the extra bolus of fentanyl in BDE. We also provided the simplified formula as propofol CeM = CeLOC + 0.7 μg/mL to avoid patient movements affecting the procedure and adverse effects.