OBJECTIVE: To compare the analgesia, sedative effect and safety of oxycodone and fentanyl after laparoscopic hysterectomy. METHODS: A total of 113 patients underwent selective laparoscopic hysterectomy during Aug. 2015-Apr. 2017 were selected and divided into oxycodone group (58 cases) and fentanyl group (55 cases) according to random number table. Oxycodone group received 0.07 mg/kg Oxycodone hydrochloride injection intravenously before skin suture. Fentanyl group received 0.7 μg/kg Fentanyl citrate injection intravenously before skin suture. The patients were given relevant drugs for patient-controlled intravenous analgesia after they woke up. Hear rate (HR), central venous pressure (CVP), mean arterial pressure (MAP) and oxygen partial pressure [p(O2)] were observed in 2 groups before analgesia induction (T0), at the moment of extubation (T1), 5 min after extubation(T2). VAS score and Ramsay sedation score were observed 1 h(T3), 6 h(T4), 12 h(T5), 24 h(T6), 48 h(T7) after surgery. The levels of serum P substance and 5-HT were observed before analgesia induction (T0), 1 h(T3), 6 h(T4), 12 h(T5), 24 h(T6), 48 h(T7) after surgery. The occurrence of ADR were recorded. RESULTS: At T1 and T2, HR and MAP of 2 groups were significantly higher than at T0, and oxycodone group was significantly lower than fentanyl group, with statistical significance (P<0.05); there was no statistical significance in the levels of CVP or p(O2) between 2 groups at different time points (P>0.05). At T3-T6, VAS score of oxycodone group was significantly lower than that of fentanyl group, with statistical significance (P<0.05). There was no statistical significance in VAS score at T7 or Ramsay score at T3-T7 between 2 groups (P>0.05). The levels of serum P substance and 5-HT in 2 groups at T3, T6 and T7 were significantly higher than at T0; at T3, T6, the oxycodone group were significantly lower than the fentanyl group, with statistical significance (P<0.05). At T7, there was no statistical significance in the levels of serum P substance and 5-HT between 2 groups (P>0.05). Total incidence of ADR in oxycodone group (12.1%) was significantly lower than fentanyl group (27.3%), with statistical significance (P<0.05). CONCLUSIONS: Oxycodone is better than fentanyl in maintaining hemodynamic stability, early reducing the serum levels of pain-induced substances, early analgesic effects for patients underwent laparoscopic hysterectomy, but sedative effect of them are similar.