Aim: The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. Materials and Methods: Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BED α/β10Gy was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. Results: At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BED α/β10Gy ≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BED α/β10Gy ≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). Conclusion: SBRT proved to be tolerable and effective in LAPC. Moreover, BED α/β10Gy ≥48 Gy was significantly correlated with improved OS and LC. Pancreatic cancer (Pca) is projected to become the second cancer killer in the United States by 2030 (1). Overall, 5-year survival in Pca patients is only 8% (2). Radical surgery achieving negative margins is the only treatment able to gain long-term survival (3, 4). Unfortunately, only a small percentage of patients (around 20%) present with a resectable tumor at diagnosis, while 30-40% of them have unresectable locally advanced disease (5). Moreover, these patients represent a category with an intermediate prognosis between resectable and metastatic disease (6), with a median overall survival (OS) ranging from 9 to 11 months (5). Nowadays, a therapeutic standard approach for Pca is missing and therefore the treatment is frequently institution 465 This article is freely accessible online.