background and Aims Large incisional hernia repair is always a matter of challenge, because the closure of large defects may likely lead to serious pathophysiological consequences or even life-threatening complications such as abdominal compartment syndrome （ACS）. The preoperative progressive pneumoperitoneum (PPP) can widen the abdominal cavity of the patients, and facilitate reduction of the hernia contents, and the botulinum toxin A (BTA) can cause revisable relaxation the abdominal wall muscles, so their combined use in preoperative preparation of large incisional hernia repair surgery is considered to produce a complementary effect. Therefore, this study was performed to evaluate the application value of PPP combined with BTA injections in large incisional hernia repair.Methods The clinical data of 7 patients with large incisional hernia undergoing laparoscopic intraperitoneal onlay mesh repair (IPOM) using the combination of PPP and BTA injections for preoperative preparation in the Sixth Affiliated Hospital of Sun Yat-sen University from June 2018 to December 2021 were retrospectively analyzed. Before operation, the patients underwent BTA injections into the lateral abdominal wall muscles and abdominal catheter insertion for the PPP under ultrasound guidance. The changes in the volumes of the incisional hernia (VIH), the volumes of abdominal cavity (VAC) and the length and thickness of the lateral abdominal wall muscle before and after PPP plus BTA treatment were measured by CT software. The adverse reactions after PPP plus BTA treatment, the intra- and postoperative complications and follow-up results were recorded.Results Among the 7 patients, 4 cases were males and 3 cases were females, with a median age of 59 (44-71) years and a median body mass index of 25.6 (21.3-31.2) kg/m²; 6 cases had primary hernia and one case had recurrent hernia; 2 cases complicated with underlying diseases. After PPP plus BTA treatment, the average increase in length of the lateral abdominal muscle on each side was 3.5 cm, the average decrease in thickness of the abdominal wall muscle on each side was 0.3 cm, the average increaseing value of VIH was 829 mL, the average increaseing value of VAC was 2 982 mL, and the average decreasing value of VIH/VAC ratio was 1.7%, respectively; varying degrees of spontaneous reduction of the hernia contents into the abdominal cavity occurred in all patients. During PPP plus BTA preparation, abdominal distention and abdominal pain occurred in 2 patients, shoulder and back pain occurred in one patient, and subcutaneous emphysema occurred in one patient, but all resolved spontaneously without special treatment. The IPOM operation was uneventfully completed in all patients, the average operative time was (186±114) min and the length of postoperative hospital stay was (6.4±1.1) d. The postoperative VAS scores for all patients were lower than 3, and no analgesic supplement was needed. After surgery, low intestinal obstruction occurred in one patient, which was relieved after symptomatic treatment, and no serious complications such as ACS occurred. The average follow-up time was (10.4±8.8) months, and no chronic pain, recurrence and mesh infection complications were observed.Conclusion PPP plus BTA treatment for preoperative preparation can significantly increase the abdominal volume of large incisional hernia and prolong the length of the lateral abdominal muscles of the patients, which is helpful for defect closure and reducing the occurrence of serous postoperative complications. So, it is recommended to be use in clinical paractice.