【Abstract】 Objective To evaluate the clinical effects of propofol respectively combined with fentanyl, remifentanil or sufentanil in anesthesia for painless gastroscopy. Methods 360 patients undergoing gastroscopy were randomly divided into four groups: F (fentanyl + propofol), R (remifentanil + propofol), S (sufentanil + propofol), C (propofol). Opioids in four groups were used in equivalent dose and the dosage of propofol in each group was 1.5 mg/kg. Anesthesia effects, onset time and duration of anesthesia with different combinations and the incidence of opioid-related side effects in each group were recorded. The subjects and observers were double-blind to this trial. Results The percentage of satisfactory anesthesia cases in the group C (only 25.6%) waslower than that in the groups F (75.6%), R (94.4%) and S (73.3%) significantly. Comparing the anesthesia onset time of each opiate, it was shorter in group R (3.90± 0.39 )s than in the group F (9.05 ±0.63) s and the group S (6.45 ±0.27) s (P < 0.05). There was no significant difference on anesthesia action time in these three groups . No severe cardiac vascular inhibition occurred in all four groups. There were no abdomen rigidity, respiratory depression and other opioid-related side effects happened in the group C. There were higher incidence of abdomen rigidity and significant desaturation (<90%) in the group R (17.78%，1.11%) when compared with the group F（4.44%，1.11%） and the group S（6.67%，1.11%） (P<0.05), but lower incidence of bucking and body movement in the group R. Conclusions In anesthesia for painless gastroscopy, more rapid onset of action, better anesthesia effect, but more opioid-related side effects were achieved by using the combination of remifentanil, but not fentanyl and sufentanil, and propofol .