In this episode of Hospital Medicine Unplugged, we cut through hospital-focused amputation decisions—prioritize life over limb, align with patient goals, and plan for function from day one. We open with the do-firsts: stabilize sepsis and perfusion, control infection with source control, tighten inpatient glucose, and stage limb threat (WIfI, GLASS). Loop in vascular, ortho/plastics, ID, endocrine, rehab, palliative, and social/behavioral health—decisions are team sport. Call amputation when absolute indications hit: uncontrolled sepsis, nonviable extremity, or metabolic derailment from necrosis. Relative cues: failed revascularization, intractable pain, nonfunctional limb, or nonambulatory baseline where salvage won’t restore independence. The diagnosis-to-decision framework:• Shared decision-making: clarify best/worst/most likely outcomes; center values (comfort vs mobility, limb image vs prosthesis function).• Select the most distal level that will heal and maximize function. Minor (toe/transmetatarsal) when feasible; escalate only when biology or biomechanics demand it.• Primary amputation for survival threats; secondary after failed salvage.• Build the post-op plan before the first cut: pain pathway (regional + multimodal), dressing/edema control, early PT/OT, discharge destination, prosthetics timeline. Level matters—function follows the joint:• Toe/forefoot: preserves gait; watch for pressure transfer and recurrence.• Midfoot (Lisfranc/Chopart) & Syme: possible but orthotics-heavy; risk of equinus/imbalance.• Below-knee (transtibial): knee preserved → highest prosthesis use and independent ambulation.• Through-knee: niche; seating advantages for some.• Above-knee (transfemoral): highest energy cost, lowest community ambulation—choose only when required. Outcomes reality check:• Mortality is high (30-day through 5-year climbs with age/comorbidity and proximal level).• Function and quality of life track with walking ability and prosthesis use; depression/anxiety are common—screen and treat.• Rehab and prosthetics access drive return to home/work more than the incision itself. Medical optimization pearls:• Resuscitate, revascularize if feasible, then operate—don’t chase salvage that endangers life.• Glycemic target ~<180 mg/dL, statin + antiplatelet unless contraindicated, smoking cessation, nutrition up.• Culture-guided antibiotics; debride early; involve ID for bone/joint disease. When salvage still on the table:• Attempt only with hemodynamic stability, manageable infection, reconstructible perfusion/soft tissue, and reasonable expectation of a pain-free, functional limb.• Bail-out early if physiology worsens, tissue demarcates proximally, or function will be inferior to amputation. Psychosocial essentials:• Name the losses, normalize grief, and offer peer support.• Embed behavioral health for depression/PTSD risk; family engagement improves clarity and follow-through.• Document goals of care and revisit as the picture evolves. System moves that change outcomes: Default multidisciplinary pathway (vascular-ID-rehab-behavioral). Objective staging (WIfI/GLASS) at consult. Life-over-limb trigger for primary amputation when unstable. Level selection huddle with prosthetist input. CRP-/trend-guided antibiotic and dressing protocols. Early mobilization + rigid/semirigid dressings for edema control. Prosthetics fast-track and scheduled socket checks. Contralateral limb surveillance and PAD secondary prevention. Quality dashboards (30-day complications, time to prosthesis, 1-year mobility) for continuous improvement. We close with the takeaway: decide fast, decide together, and decide for the whole patient—survival first, then the most distal level that heals, wrapped in rehab, psychosocial support, and lifelong vascular prevention.