Objective To explore the effect of multimodal pain management in the perioperative period of ambulatory laparoscopic cholecystectomy. Methods Non-randomized historical control method was adopted. Patients who underwent laparoscopic cholecystectomy in the Day Surgery Center of West China Hospital, Sichuan University were included. The patients who received single modal pain management between January and May 2020 were taken as the control group, and the patients who received multimodal pain management between January and May 2021 were taken as the trial group. The postoperative pain and pain-related indicators of the two groups were compared. Results A total of 731 patients were included, including 496 in the trial group and 235 in the control group. There was no significant difference in gender, age, body mass index, nationality, education level, diagnosis, marriage and occupation between the two groups (P>0.05). There were 41 patients with moderate or above pain after surgery in the trial group, of which 3 patients were accompanied by severe nausea and vomiting. There were 41 patients with moderate or above pain after surgery in the control group, of which 4 patients were accompanied by severe nausea and vomiting. The incidence of moderate or above postoperative pain (8.3% vs. 17.4%) and post-discharge pain (0.0% vs. 1.3%) in the trial group were lower than those in the control group (P<0.05). There was no significant difference in the incidence of postoperative severe nausea and vomiting and delayed discharge due to postoperative pain between the two groups (P>0.05). There was no statistically significant difference between the two groups patients with moderate or above pain in gender, age, body mass index, education level, diagnosis, time from the onset of pain to the end of surgery, pain location, pain nature, use rate of antiemetic drugs, and score after treatment (P>0.05). The majority of pain sites were surgical incision pain, and the nature of pain was mostly swelling pain. The pain score of patients with moderate or above pain in the trial group was lower than that of the control group (4.4±0.6 vs. 4.9±1.1, P<0.05). Conclusion Multimodal pain management reduces postoperative pain of patients undergoing ambulatory laparoscopic cholecystectomy by means of assessment, medication, procedure improvement, health education, which can provide guarantee for perioperative quality management of ambulatory laparoscopic cholecystectomy.