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Efficacy of single-shot opioid spinal analgesia after pancreatoduodenectomy remains understudied and lacks comparison to standard continuous thoracic epidural analgesia (TEA).Pancreatoduodenectomy patients who underwent TEA or opioid spinal for postoperative pain management from 2015 to 2020 were included in this observational cohort study. Primary outcome was patient-reported mean daily pain scores. Secondary outcomes included postoperative morphine milligram equivalents (MMEs) and length of stay (LOS). Multivariable linear regression models were constructed to compare risk-adjusted outcomes.180 patients were included: 56 TEA and 124 opioid spinal. Compared to epidural patients, opioid spinal patients were more likely to be older (67.0 vs. 64.6, p=0.045), have greater BMI (26.5 vs. 24.4, p=0.02), and less likely to be smokers (19.4% vs. 41.1%, p=0.002). Opioid spinal, compared to TEA, was associated with lower intraoperative MMEs (0.25 vs. 22.7, p0.001) and postoperative daily MMEs (7.9 vs. 10.3, p=0.03) on univariate analysis. However, after multivariable adjustment, there was no difference in average pain scores across the postoperative period (spinal vs. epidural: 4.18 vs. 4.14, p=0.93), daily MMEs (p=0.50), or LOS (p=0.23).There was no significant difference in postoperative pain scores, opioid use, or LOS between patients managed with TEA or opioid spinal after pancreatoduodenectomy.