Objective To explore the clinical value of preoperative neoadjuvant chemotherapy (NAC) combined with laparoscopic pancreatoduodenectomy (LPD) with multiple surgical approaches in the treatment of borderline resectable pancreatic head cancer. Methods The clinicopathologic data of 35 patients with critical resectable pancreatic head carcinoma admitted to the Department of Hepatobiliary and Pancreatic Surgery of Luoyang Central Hospital Affiliated to Zhengzhou University and the Department of Hepatobiliary and Pancreatic Surgery of the Fifth Affiliated Hospital of Zhengzhou University from January 2017 to June 2022 were retrospectively analyzed. All patients received NAC before operation (AG protocol). At the end of the course of treatment, according to the type of borderline resectable pancreatic cancer (BRPC) [venous invasion type (BRPC-V type) and arterial invasion type (BRPC-A type)], take the individualized surgical approach for LPD (BRPC-V type: inferior mesenteric vein approach; BRPC-A type: left posterior approach, medial uncinate process approach, anterior approach, or lower mesocolon approach). The intraoperative condition, R0/R1 resection rate, lymph node dissection, postoperative complications, average hospital stay, recovery, follow-up and survival were recorded. Results① Efficacy evaluation of NAC: 13 patients were partially relieved , 17 patients were stable and 5 patients were progressive after 4 weeks of treatment. Five progressive patients continued to receive comprehensive internal medicine treatment, and the remaining 30 patients underwent LPD. ② Intraoperative situation: LPD were successfully completed in 30 patients, 2 patients underwent extended pancreaticoduodenectomy combined with superior mesenteric vein (or) portal vein reconstruction among them. Among the 30 patients with LPD, there were 10 cases of inferior mesenteric vein approach, 10 cases of left posterior approach, 6 cases of medial uncinate process approach, 1 case of left posterior approach+medial uncinate process approach, 2 cases of anterior approach, and 1 case of inferior mesocolon approach. The mean operative time was (379.4±77.3) min, the intraoperative blood loss was (436.9±95.1) mL. ③ Postoperative situation: The incidence rate of postoperative surgery-related complications was 33.3% (10/30), including 4 cases of Clavien-Dindo grade Ⅰ [biliary fistula in 1 case (3.3%), A-grade pancreatic fistula in 1 case (3.3%), gastric draining dysfunction in 1 case (3.3%), diarrhea in 1 case (3.3%)], 5 cases of grade Ⅱ [pulmonary infection in 2 cases (6.6%), B-grade pancreatic fistula in 2 cases (6.6%), abdominal infection in 1 case (3.3%)], and 1 case of grade Ⅲ [gastroduodenal artery stump bleeding (3.3%)]. Among the 10 patients with complications, 9 cases recovered after symptomatic treatment, and 1 case died, with a fatality rate of 3.3% (1/30). The mean postoperative hospital stay was (17.3±5.5) days. ④ Excision rate and pathological results: R0 resection rate was 90.0% (9/10) in 10 patients with BR-PV type LPD, and R1 resection was performed in 1 patient. R0 resection rate was 75.0% (15/20) in 20 patients with BR-A type, and R1 resection was performed in 5 patients (2 patients with medial uncinate process approach; Left posterior approach in 2 cases; Submesocolon approach was used in 1 case). In 30 patients with LPD, the total R0 removal rate was 80.0% (24/30), the number of lymph nodes dissected was (11±5). Pathological type: There were 26 cases (86.7%) of ductal adenocarcinoma in 30 patients, 1 case of adeno-squamous carcinoma (3.3%), 1 case of mucinous carcinoma (3.3%), 2 cases of acinocytic cell carcinoma (6.7%). 23 cases (76.7%) of medium-high differentiation and 5 cases (16.6%) of low differentiation, two cases (6.7%) were undifferentiated. ⑤ Postoperative follow-up and survival: 30 patients were completely followed-up for 6-39 months, with a median follow-up time of 17 months. The median survival time of BRPC-V and BRPC-A patients was 24.0 months and 17.0 months, respectively. The overall survival rates of 30 patients at 1, 2 and 3 years after operation were 77.3%、46.5% and 13.7%, respectively. Conclusion The selection of preoperative NAC combined with individualized surgical approach for patients with borderline resectable pancreatic head cancer is beneficial to improve the radical resection rate and clinical therapeutic effect, and has good clinical application value.