Abstract Background Postoperative pancreatic fistula (POPF) is responsible of most major complications and fatalities after PD. By avoiding POPF, TP may improve operative outcomes in high‐risk patients. The aim was to compare total pancreatectomy (TP) and pancreatoduodenectomy (PD) in high‐risk patients and evaluate results of implementing a risk‐tailored strategy in clinical practice. Methods Between 2014 and 2023, 139 patients (76 men, median age 67 years) underwent resection of disease located in the head of the pancreas. Starting January 1, 2022, we offered TP to patients at high POPF risks (fistula risk score (FRS) ≥7) and to patients with intermediate POPF risks (FRS: 3–6) and high risks of failure to rescue (age> 75 years, ASA score ≥3). We compared outcomes of TP and PD and evaluated the results of the new strategy implementation on operative outcomes. Propensity score–based analysis was performed to limit bias of between‐group comparison. Results Eventually, 26 (19%) patients underwent TP and 113 (81%) patients underwent PD. Severe complications occurred in 42 (30%) patients and 13 (9%) patients died. TP resulted in shorter lengths of hospital stay (median: 14 days [11; 18] vs. 17 days [13; 24], p = 0.016) and less risks of post‐pancreatectomy hemorrhage (PPH) (0% vs. 20%, p < 0.001) compared to PD. Crude and propensity match analysis showed that the implementation of a risk‐tailored strategy led to significant reduction of reoperation, POPF, PPH and mortality rates. Conclusion The use of TP as part of a risk‐tailored strategy in high‐risk patients can be lifesaving.