Background and Aims With the development of multidisciplinary treatment modalities and the rise of precision medicine, there is a general consensus that neoadjuvant therapy (NAT) can improve the radical resection rate of non-metastatic pancreatic cancer. However, due to the lack of conclusive randomized controlled trials, its role in resectable and borderline resectable patients is still controversial. Therefore, this study was conducted to compare the effectiveness and safety of surgical resection after NAT versus upfront surgery in resectable or borderline resectable pancreatic cancer patients using a Meta-analysis approach, so as to provide evidence-based reference for clinical practice.Methods Randomized controlled trials (RCTs) on NAT and upfront surgery for resectable or borderline resectable pancreatic cancer were searched from several domestic and international databases. The search time limit was from the establishment of the database to November 29, 2022. Cochrane systematic review method was used to evaluate the included studies, and RevMan 5.4 software was used for Meta-analysis of homogeneous studies.Results A total of 7 RCTs with 938 patients were finaly included. Among them, there were 466 patients in NAT group and 472 patients in upfront surgery group. The results of Meta-analysis showed that compared with upfront surgery group, the NAT group had an increased R₀ resection rate (RR=1.65, 95% CI=1.35-2.02, P<0.000 01), a decreased incidence of positive lymph nodes (RR=0.67, 95% CI=0.52-0.85, P=0.001), and a decreased surgical resection rate (RR=0.91, 95% CI=0.84-0.98, P=0.02), while there was no statistically significant difference in median survival time (MD=4.95, 95% CI=-3.26-13.15, P>0.05) or the incidence of surgical complications (RR=1.19, 95% CI=0.97-1.46, P>0.05).Conclusion For resectable or borderline resectable pancreatic cancer, NAT can increase the R₀ resection rate, reduce the incidence of positive lymph nodes, and decrease the surgical resection rate. Whether NAT can improve the overall survival rate of patients with resectable or borderline resectable pancreatic cancer still needs to be verified by more high-quality multicenter randomized controlled studies.