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Background Cancer-related inflammation is a distinctive feature of the development and progression of PC. However, the relationship between the systemic inflammatory response and survival has not been evaluated as a predictive factor of chemotherapy. The aim of this study was to evaluate the prognostic and predictive value of a baseline SIRI based on peripheral neutrophil, monocyte, and lymphocyte counts in metastatic PC. Methods Retrospective review of 178 metastatic pancreatic cancer patients. Associations between overall survival (OS), time to progression (TTP), chemotherapy schedule and SIRI at diagnosis were analyzed. Results Median age 67 years, 52% were male. First line chemotherapy regimens: 41% Gemcitabine, 31% Gemcitabine plus Nab-Paclitaxel and 17% mFOLFIRINOX. Patients with SIRI Conclusions An elevated SIRI (≥2.3x109) is an independent prognostic factor for survival in patients with metastatic pancreatic cancer. Patients with an elevated SIRI (≥2.3x109) show an increased benefit from mFOLFIRINOX in comparison to other first line chemotherapy regimens. These results raise the issue of appropriately selecting patients who would benefit of a more intensive first-line chemotherapy regimen. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.