Background: Indication for pancreatoduodenectomy for pancreatic cancer can be challenging. Wrong decisions in indication processes lead to significant health impairments. Computerized decision support systems can take over parts of decision-making processes, making them more accurate. MEBDAS® is a decision-supporting software that predicts outcomes of proposed treatments. Aim: to determine the decision concordance between MEBDAS® and multidisciplinary tumour board (MTB) and the impact of MEBDAS® on in-hospital outcome at different indication thresholds. Methods: 126 patients with pancreatoduodenectomy from a high-volume university hospital were included. Outcome indicators were in-hospital mortality, Comprehensive Complication Index (CCI®), therapy-related loss of “Quality-Adjusted-Life-Day” (QALD-loss) and prognostic gain of treatment-related “Quality-Adjusted-Life-Year” (QALY-gain). Results: The concordance of decisions was 94.4% at the indication threshold of 0. By raising the indication threshold to 1 year, the concordance decreased to 0%, the in-hospital-mortality dropped from 2.52% to 0%, the CCI® decreased from 26.47 to 13.90, the therapy-related QALD-loss declined from 21.53 to 16.22 days and the prognostic QALY-gain increased from 0.374 to 0.906 years. At IT = 0.250 years, the concordance was 61.11% and differences between MTB and MEBDAS®-group were highly significant (p < 0.001) for all outcome parameters: mortality (3.97% vs. 1.30%), CCI® (28.96 vs. 18.29), therapy-related QALD-loss (24.41 vs. 15.19 days) and QALY-gain (0.351 vs. 0.501 years). Conclusion: MEBDAS® decisions are superior to those of MTB in terms of in-hospital-outcome. The inclusion of MEBDAS® in decision procedure makes the indication more accurate and reduces morbidity and mortality. In addition, MEBDAS® can increase patients’ competence by involving them in decision-making process.