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Objectives: Opioids are commonly used for pain control after lower extremity amputations (LEA)—below the knee amputations (BKA) and above the knee amputations (AKA). Well-defined benchmarks for prescription requirements after amputation are deficient. This analysis evaluated opioid utilization after amputation to identify high-risk patients and provide recommendations for post-hospitalization opioid prescriptions at discharge. Methods: Patients undergoing LEA (2008–2016) with identified peripheral vascular disease were selected from Cerner's Health Facts® database using ICD-9 and 10 diagnosis and procedure codes. Patient demographics, disease severity, comorbidities, and hospital characteristics were evaluated. Post-operative opioid medications administered intravenously and orally during the hospital stay were identified from the data and converted to Morphine Milligram Equivalent per day (MME/d) for an evaluation and comparison during the index hospitalization. Descriptive statistics were used to report continuous and dichotomous variables. Dichotomous variables are reported as n (%) and continuous variables are reported as mean ± standard deviation (SD). Chi-square and T-tests were used as appropriate. Results: 2399 patients who underwent AKA or BKA with peripheral vascular disease were evaluated. Sixty-three percent of the cohort was male, 67% Caucasian, and 42% married, and 58% had a Charlson index >3. The majority of patients had an average length of hospital stay of 5.7 days (M = 5.72, SD = 4.56). Patient groups that used significantly higher MME/d in the early postop period included: BKA (29.2 vs 20.7, p = 0.006), males (62.6 vs 54.0, p < 0.0001), Caucasians (64.3 vs 44.7, p < 0.0001), younger patients (69.6 vs 54.0, p < 0.0001), and those at non-training institutions (66.7 vs 56.7, p < 0.0001). Patients whose hospital stay was greater than 6 days were found to have increased opioid utilization likely secondary to index complications. For those discharged by post-operative day 7, the mean MME utilized on postop day 1 was 59.5 and decreased to a mean MME/d utilization prior to discharge of 17.6. Conclusions: This analysis demonstrates that younger patients, males, patients with BKAs, and those who receive amputations for vascular disease at non-training institutions have higher post-operative opioid utilization during the hospital stay. At the time of discharge, patients utilized an average of 17.6 MME/d which equates to approximately three hydrocodone/acetaminophen 5/325 mg tablets per day. Based on these findings, vascular surgeons are likely over prescribing opioids at discharge and must be cognizant of appropriate dosing quantities. Prescriptions at discharge should reflect the daily utilization described from this analysis and tapered to avoid chronic utilization, overdose, and possible death. [ABSTRACT FROM AUTHOR]