Objective To compare the analgesic effects of fentanyl, tramadol and flurbiprofen axetil during vitrectomy under local anesthesia. Methods One hundred and twenty patients who underwent vitrectomy were randomly divided into four groups, 30 patients in each group. Control group (Group C): normal saline were given; Fentanyl group （group F): fentanyl 1 mu;g/kg; Tramadol group （group T): tramadol 1 mg/kg; Flurbiprofen group （group K): flurbiprofen axetil 1 mg/kg. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), sedation classification (OAA / S) and pain score (NRS) were recorded prior to drug administration (T0) and the beginning of surgery (T1), 5 min (T2), 15 min(T3), 30 min (T4) and the end of surgery (T5) . The incidence of analgesic remedy and adverse reactions were also recorded after surgery. Results In group F, MAP at T1 and T2 were significantly lower than T0 and that of the other three groups at the same time point (F=5.367,5.967;P＜0.05). MAP at each time point of the other three groups had no significant changes (P＞0.05). In Group C, HR decreased significantly at T3and T4compared to T0 (F=7.900, 6.767;P＜0.05). In Group F, HR decreased significantly at T2 compared to T0 (F=3.117，P＜0.05). HR at each time point of group T and group K had no significant changes (P＞0.05). In group F, SpO2at T1 was significantly lower than T0 and that of the other three groups at the same time point (F=7.352, P＜0.05). SpO2of group F, group T and group K had no significant changes within groups (P＞0.05). In Group F, the median of OAA / S classification at T1 were grade four, which were lower than that at T0 and that of the other three groups at the same time point (chi;2=12.935, P＜0.05). There was no significant changes of the median of OAA / S classification at each time point in the other three groups (P＞0.05). In group C, the median of NRS score was three at T1 and was two at T2 respectively, which were higher than that at T0 and that of Group F and group T at the same time point (chi;2=13.748,11.616; P＜0.05). There were no significant changes of the median of NRS score in group F, group T and group K within groups (P＞0.05). Analgesic remedy percentages in group C, group F, group T and group K were 16.7%, 3.3%, 3.3%, 6.7%, respectively. The incidence of adverse reactions in group C, group F, group T and group K were 30.0%、23.3%、3.3%、16.7%, respectively.Conclusion Tramadol had efficient analgesic effects and low rate of adverse reactions during vitrectomy under local anesthesia.