OBJECTIVE： To compare the anesthetic effect and safety of propofol respectively combined with nalbuphine hydrochloride， dezocine or fentanyl for painless gastroscopy. METHODS： 180 patients undergoing painless gastroscopy were randomly divided into group A （60 cases）， group B （60 cases） and group C （60 cases）. All patients forbidden to eat 6 h and drink 4 h before surgery， no premedication. Opening veins after entering the room， multi-function ECG monitor was used to monitor the systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， pulse oxygen saturation （SpO2）， intravenously infused 0.9% Sodium chloride injection， oxygen inhalation for 3 L/min by nasal catheter. Based on it， group A intravenously injected Nalbuphine hydrochloride injection 0.15 mg/kg+Propofol injection 1.5 mg/kg； group B intravenously injected Dexorcin injection 5 mg+ Propofol injection 1.5 mg/kg； group C intravenously injected Sufentanil injection 5 μg+Propofol injection 1.5 mg/kg. According to patients’ body movement and swallowing reflex， all patients added 20-30 mg Propofol injection to maintain the depth of anesthesia. SBP， DBP， HR and SpO2 before anesthesia （T0）， after eyelash reflex disappeared （T1）， after placing gastroscopy （T2） and when came to senses （T3）， awakening time and discharge time， MMSE score before and after anesthesia， and the incidence of adverse reactions in each group were observed. RESULTS： The SBP， DBP， HR and SpO2 in each group at T1-3 were significantly lower than T0， SpO2 at T1 in group C was lower than group A and group B， with statistical significances （P＜0.05）， while there was no significant difference in group A and group B. There were no significant differences the above-mentioned indexes in each group at T1-3（P＞0.05）. The discharge time in group A was significantly shorter than group B， with statistical significance （P＞0.05）， there was no significant difference in group A and group C， group B and group C （P＞0.05）. The intraoperative cough rate and incidence postoperative nausea and vomiting in group A were significantly lower than group B and group C， with statistical significances （P＜0.05）， while there was no significant difference in group B and group C （P＞0.05）； the incidences of dizziness and drowsiness in group A and group C were significantly lower than group B， with statistical significances （P＜0.05）， there was no significant difference in group A and group C （P＞0.05）， and there was no significant difference in the incidence of intraoperative body movement in each group（P＞0.05）. And there was no significant differences in awaking time and the MMSE scores before and after anesthesia in each group （P＞0.05）. CONCLUSIONS： Propofol combined with nalbuphine has better anesthetic effect and safety than dexorcin and sufentanil for painless gastroscopy.