Background and Aims The repair of giant incisional hernia is challenging, as closing the significant defect in the abdominal wall can lead to life-threatening complications like abdominal compartment syndrome (ACS). Botulinum toxin type A (BTA) can temporarily relax the abdominal wall muscles, facilitating defect repair, while preoperative progressive pneumoperitoneum (PPP) can increase intra-abdominal volume, reducing intra-abdominal pressure caused by hernia content reintegration. Combining BTA with PPP for the preoperative preparation of giant incisional hernia repair may have a complementary effect. This study was conducted to evaluate the clinical value of combining BTA and PPP in the repair of giant abdominal incisional hernia.Methods The clinical data of 213 patients with giant abdominal incisional hernia treated at the Sixth Affiliated Hospital of Sun Yat-sen University from December 2015 to December 2019 were retrospectively analyzed. Two weeks after receiving combined BTA and PPP treatment, changes in bilateral abdominal wall muscle, intra-abdominal adhesions, abdominal circumference, abdominal cavity volume, and hernia sac volume ratio were assessed using CT. Intraoperative details, incidence of complications, and postoperative follow-up outcomes were recorded.Results Following combined BTA and PPP treatment, CT scan showed a significant extension of bilateral lateral abdominal wall muscles towards the midline in all 213 patients, with an average increase of 2.45 (1.53-3.29) cm on the left side and 2.54 (1.68-3.40) cm on the right side; muscle thickness was reduced by an average of 0.84 (0.64-1.00) cm on the left and 0.82 (0.62-1.05) cm on the right, the average distance between viscera and the abdominal wall increased to (7.52±1.78) cm, with a mean increase of 6.1 (4.2-6.9) cm; the mean increase in abdominal cavity volume was 1 802 (1 494.98-2 316.26) mL, and the hernia sac volume ratio decreased by an average of 9% (6%-12%), all changes were statistically significant (P<0.05). Post-PPP CT scan revealed no abdominal adhesions in 18 patients (8.45%), while 195 patients (91.55%) had varying degrees of adhesions, including 39 cases (18.31%) of sheet adhesions and 156 cases (73.24%) of mixed adhesions. Adhesions mainly consisted of omentum and intestinal tissues in 59.15% of cases. There were 43 cases (20.19%) of grade I complications during the BTA-PPP process, including abdominal pain (28 cases), shoulder pain (9 cases), subcutaneous emphysema (6 cases), and dyspnea (3 cases). Dyspnea improved with oxygen therapy, while other complications required no special intervention. All 213 patients successfully underwent laparoscopic incisional hernia repair without conversion to open surgery or organ resection for volume reduction. Fascial closure was achieved in 209 cases (98.12%), with 4 cases (1.88%) having incomplete defect closure. The average time for adhesiolysis was 28 (11.00-44.50) min, with a total operative time of 178.0 (132.50-255.00) min and an average blood loss of 20 (10-30) mL. The median intra-abdominal pressure (IAP) after operation was between 10 mmHg (9.00-12.00 mmHg), Among them, 47 cases (22.07%) had IAP exceeding 12 mmHg, and after implementing proactive measures such as diuresis and diachoresis to reduce intra-abdominal contents, the IAP in these patients decreased to below 12 mmHg. No severe complications such as skin flap necrosis or ACS were observed. There were no deaths within postoperative 30 d, and during a follow-up period of 26 (16.50-33.00) months, 13 cases (6.10%) had surgical site events, including infections in 5 cases (2.35%), seromas in 7 cases (3.29%), and hematoma in 1 case (0.47%), with no hernia recurrence.Conclusion The combination of BTA and PPP not only aids in identifying abdominal wall adhesion areas, improving preoperative surgical planning and enhancing surgical safety, but also significantly increases abdominal cavity volume and extends lateral abdominal wall muscles, facilitating the closure of giant incisional hernia defects and reducing the incidence of severe postoperative complications like ACS. This approach is worthy of clinical promotion.