【Abstract】 objective To compare the efficacy of oxycodone or fentanyl combined with dexmedetomidine during flexible ureteroscopic lithotripsy. Methods 90 patients with flexible ureteroscopic lithotripsy in our hospital from March 2014 to March 2016 were selected and randomly divided into three groups, n=30. GroupⅠ: fentanyl1ug/kg + dexmedetomidine 1.0ug/kg, groupⅡ: oxycodone 0.05mg/kg + dexmedetomidine 1.0ug/kg, groupⅢ: oxycodone 0.1mg/kg + dexmedetomidine 1.0ug/kg. Dexmedetomidine 1.0ug/kg intravenous infusion in every group before skin incision in10mins. meanwhile, Oxycodone 0.05mg/kg, 0.1mg / kg and fentanyl 1ug / kg were intravenous in three groups, respectively. The changes of hemodynamic, ureteroscopy stimulation grading and adverse events were compared in three groups during surgery. Results The blood pressure of group Ⅲ is lower than of the Ⅰ group when flexible ureteroscopy get through the urethra、ureter and gravel(P <0.05), the blood pressure of group Ⅲ is lower than of the group Ⅱwhen flexible ureteroscopy get through the urethra and ureter (P <0.05). The ratio of gradeⅠstimulation in group Ⅱand group Ⅲ was more than that of groupⅠ(P＜0.05 or P＜0.001), the ratio of gradeⅡand Ⅲ was less than that of groupⅠ(P＜0.05). The ratio of cough and respiratory depression in group Ⅱ and Ⅲwas less than that in groupⅠ(P＜0.05 or P＜0.01). Conclusions Oxycodone 0.1mg/kg combined with dexmedetomidine can decrease the irritation of flexible ureteroscopic lithotripsy and adverse reactions than that of fentanyl.