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Introduction: despite significant medical and technological advances, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) is reported to be between 3-45 %. The main objective of this study was to analyze the early post-surgical risk factors for developing POPF after DP., Material and Methods: a retrospective observational study was performed on a prospective basis of patients undergoing DP in a tertiary hospital from January 2011 to December 2021. Sociodemographic, preoperative analytical, tumor-related and postoperative complications variables were analyzed., Results: of the 52 patients analyzed, 71.8 % of the sample had postoperative drains amylase elevation. However, 25.7 % of the total had grade-B and/or grade-C POPF. Univariate logistic regression with the variables studied showed the following as risk factors for B-C or clinically relevant POPF: amylase values in drainage at the 5th postoperative day (POD) (p = 0.097; 1.01 [1-1.01]), preoperative BMI (p = 0.015; 1.27 [1.04-1.55]) and C-reactive protein (CRP) value at the 3rd POD (p = 0.034; 1.01 [1.01-1.02]). The ROC curve of CRP value at the 3rd POD showed an area under the curve of 0.764 (95 % CI: 0.6-0.93) and the best cut-off point was 190 mg/l (sensitivity 89 % and specificity 67 %)., Conclusions: CRP value at the 3rd POD is a predictive factor for POPF after DP. Early detection of patients at risk of POPF based on these characteristics could have an impact on their postoperative management.