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Please confirm that an ethics committee approval has been applied for or granted: Yes: I’m uploading the Ethics Committee Approval as a PDF file with this abstract submissionBackground and Aims Amputation patients commonly suffer from chronic ischemic limb pain followed by immediate moderate to severe postoperative pain. The aim of this study was to compare pain management strategies that replace opioids and evaluate their effectiveness, advantages, and limitations.Methods In a randomised prospective study 58 patients undergoing above the knee amputation due to vascular disease were enrolled and randomized into two groups: spinal (SA; n=30) or general anesthesia (GA; n=28). Afterward, six subgroups were compared: suprainguinal fascia iliaca block (sFIB), epidural analgesia (EA) or esketamine i/v infusion (esKET) for the first 24 hours. All patients received multimodal analgesics. The primary outcomes were postoperative pain intensity (NRS scale); secondary - opioid consumption and incidence of breakthrough pain (NRS>7) in the first 24 hours.Results Pain intensity in the first 24 hours postoperatively was observed as low to moderate (NRS 0–6). We found no significant difference in opioid (fentanyl, mean dose 40 mcg/h) consumption between groups received SA versus GA. Totally 13.7% (8/58) of patients received opioids in the first 6–12 hours after surgery due to breakthrough pain, most of whom were in SA group + sFIB. Noneone with EA or esKET experienced brakthrough pain. All patients were observed in ICU for the first 24 hours.Conclusions Perioperative pain management after lower limb amputation is indeed complex and challenging. Our applied analgesia methods in the context of multimodal approach were not equally effective demonstrating higher incidence of breakthrough pain and need for opioids in spinal anesthesia group combined with fascia iliaca block.