The use of risk-stratified pancreatectomy care pathways (RSPCPs) is associated with reduced length of stay (LOS). This study sought to evaluate the impact of successive pathway revisions with the hypothesis that high-risk patients require iterative pathway revisions to optimize outcomes. A prospectively maintained database (October 2016 to December 2021) was evaluated for pancreaticoduodenectomy patients managed with RSPCPs preoperatively assigned based on postoperative pancreatic fistula (POPF) risk. Launched in October 2016 (version [V] 1), RSPCPs were optimized in February 2019 (V2) and November 2020 (V3). Targeted pathway components included earlier nasogastric tube removal, diet advancement, reduced intravenous fluids and opioids, institution-specific drain fluid amylase cutoffs for early day 3 removal, and patient education. Primary outcome was LOS. Secondary outcomes included major complication (Accordion grade 3+), POPF (International Study Group for Pancreatic Surgery Grade B/C), and delayed gastric emptying (DGE). Of 481 patients, 234 were managed by V1 (83 high-risk), 141 by V2 (43 high-risk), and 106 by V3 (43 high-risk). Median LOS reduction was greatest in high-risk patients with a 7-day reduction (pre-RSPCP, 12 days; V1, 9 days; V2, 7 days; V3, 5 days), compared with low-risk patients (pre-pathway, 10 days; V1, 6 days; V2, 5 days; V3, 4 days). Complications decreased significantly among high-risk patients (V1, 45%; V2, 33%; V3, 19%; p < 0.001), approaching rates in low-risk patients (V1, 21%; V2, 20%; V3, 14%). POPF (V1, 33%; V2, 23%; V3, 16%; p < 0.001) and DGE (V1, 23%; V2, 22%; V3, 14%; p < 0.001) improved among high-risk patients. Risk-stratified pancreatectomy care pathways are associated with reduced LOS, major complication, Grade B/C fistula, and DGE. The easiest gains in surgical outcomes are generated from the immediate improvement in the patients most likely to be fast-tracked, but high-risk patients benefit from successive application of the learning health system model.