Abstract: Objective To investigate the analgesic effect and safety of intravenous oxycodone combined with transversus abdominis plane block (TAPB) for multimodal analgesia in obese patients undergoing gynecological laparoscopic surgery during the perioperative period. Methods A total of 60 female obese patients who were scheduled for gynecological laparoscopic surgery at Xuzhou Maternal and Child Health Hospital from January 2023 to March 2024 were selected. They were randomly divided into two groups (n=30): an oxycodone group and a sufentanil group. Both groups underwent the same bilateral TAPB under anesthesia monitoring. Before anesthesia induction, the oxycodone group was intravenously injected with oxycodone at 0.1 mg/kg, while the sufentanil group received an intravenous injection of sufentanil at 0.1 μg/kg. The same anesthesia induction and intraoperative anesthesia maintenance protocols were performed in both groups. Then, 20 min before the end of the surgery, the oxycodone group received oxycodone at 0.1 mg/kg, while the sufentanil group was administered with sufentanil at 0.1 μg/kg. Their operation duration, time to emergence, time to extubation and time to recovery of orientation, and the length of post-anesthesia care unit (PACU) stay were recorded. The Aldrete scores at different time points after extubation in the PACU were recorded, and adverse reactions such as respiratory depression, agitation, dizziness, nausea, and vomiting during emergence were observed and recorded. The Visual Analog Scale (VAS) scores was used to assess the somatic and visceral pain at different postoperative time points. The number of cases requiring rescue analgesia within 24 h after surgery was recorded. Results The oxycodone group showed shorter times to emergence, extubation and orientation recovery, and length of PACU stay than the sufentanil group (P<0.05). During the PACU monitoring period, the oxycodone group showed decreases in the incidences of respiratore depression, agitation, nausea, and vomiting, compared with the sufentanil group (P<0.05). Within the PACU, the oxycodone group showed higher Aldrete scores than the sufentanil group at each post- extubation time points (P<0.05), and there was no statistical difference in Aldrete scores at the time of discharge from the PACU between the two groups (P>0.05). There was no statistical difference in VAS scores for somatic pain at each postoperative time point between the two groups (P>0.05). At post-operative 2 h, 6 h and 12 h, the VAS scores for visceral pain in the oxycodone group were lower than those in the sufentanil group (P<0.05). The percentage of cases requiring rescue analgesia within 24 h after surgery in the oxycodone group decreased, compared with the sufentanil group (P<0.05). Conclusions The multimodal analgesia strategy of intravenous oxycodone combined with TAPB can be applied in obese patients during gynecological laparoscopic surgery, with fast and high-quality emergence and effective postoperative analgesia for visceral pain.