Abstract：Objective To compare the efficacy and safety of oxycodone combined with dexmedetomidine versus hydromorphone for postoperative analgesia after cesarean section. Methods A total of 200 parturients undergoing elective cesarean section in Guilin Women and Children's Hospital from June 2023 to June 2024 were randomly divided into observation group  （oxycodone analgesia）and control group（hydromorphone analgesia）, with 100 cases in each group. Incision pain scores, uterine contraction pain scores at different time points after operation, incidence of adverse reactions, and neonatal neurobehavioral scores were compared between the two groups. Results There were no significant differences in incision pain scores and neonatal neurobehavioral scores at each postoperative time point between the two groups（t＝0.924, 0.481, 0.370, 0.781, 0.905, 0.381, 0.503, 0.734, all P＞0.05）. Uterine contraction pain scores at 6, 12, and 24 h postpartum in the observation group were lower than those in the control group, with statistically significant differences（t＝2.531, 2.704, 4.981, all P＜0.05）. The incidence of adverse reactions in the observation group was also significantly lower than that in the control group, and the difference was statistically significant（χ2＝4.421, P＜0.05）. Conclusion Oxycodone combined with dexmedetomidine provides satisfactory analgesic effects after cesarean section. It can better relieve both incision pain and uterine contraction pain, with a lower incidence of adverse reactions and less impact on newborns, indicating high overall safety.