Pancreatic adenocarcinoma (PDAC) represents the fourth cause of death-related mortality in Italy. Only 20 % of patients have with resectable tumors at diagnosis. The introduction of new chemoterapic regimens (folfirinox (FFN) and gemcitabine-paclitaxel (GEMPAC)) has brought to encouraging improvements in downstaging, conversion to resectability and overall survival. The aim of the study was to evaluate the impact of neoadjuvant therapy (NAT) in “borderline resectable” (BR) and locally advanced pancreatic adenocarcinoma (LAC). We enrolled all patients with BR and LAC PDAC from January 2012 to December 2020. Survival data were estimated with the Kaplan–Meier method and examined using the log-rank test. The most frequent chemoterapic regimens were FFN and GEMPAC, in the 51,06% and 36,17% of cases, respectively. After NAT, 20% of patients were resected with a DSF of 26,43 ± 5,51 months. The OS in the entire cohort was 19,82 ± 2,21 months. The OS of the different groups of patients was: 5,66 ± 1,96 months for patients undergoing to best supportive care; 14,29 ± 2,09 months for patients experiencing progression of disease; 19,82 ± 3,07 months for patients undergoing surgical exploration but not resection and 40,44 ± 4,27 months for resected patients. The use of chemoterapic regimens other than FFN and GEMPAC was associated to progression of disease and a poor OS (p<0,05). The multivariate analysis of risk factors influencing OS showed that lymph-node involvement and an increased CA 19.9 after NAT were associated to a poor OS (p<0,05). Data reported in the Literature suggest that the use of FFN and GEMPAC represents a key point in the treatment of BR and LAC PDAC. However, the response rates are variable and they do not always correlate with the surgical resectability., New randomized clinical trails are necessary to establish the role of the different therapies available.