Background: Calciphylaxis is most commonly seen in end-stage renal disease and hemodialysis (uremic calciphylaxis). Nonuremic calciphylaxis is described, but large studies are lacking. Design: All calciphylaxis cases from 2010-2019 were identified. Uremic calciphylaxis cases (patients with ESRD, chronic kidney disease with creatinine level ≥ 3 mg/dl, acute kidney injury requiring renal replacement therapy or transplantation) were excluded. Charts and available biopsies were reviewed. Results: 24/68 (35%) were nonuremic calciphylaxis. Median age was 66 years (range 31-88) with an F: M ratio of 11:1. 19/24 (79%) had BMI >30 (median, 35.75). Patients presented with ulcers (17), retiform purpura (4) or indurated plaques (3) involving the thigh (9), lower leg (7), calf (6), abdomen (2), and axilla (1) Most had multiple medical conditions, including hypertension (19), diabetes mellitus (12), hyperlipidemia (10), autoimmune diseases (8), coronary artery disease (7), deep vein thrombosis (4), and atrial fibrillation (4). 3 had hyperparathyroidism at presentation. All had multiple medications, including diuretics (15), warfarin (11), antiplatelet drugs (10), corticosteroids, statins, opioids (8) and vitamin D supplements (14). Five had corrected serum calcium level > 10 mg/dl (median, 9.51 mg/dl). Seven had elevated parathyroid hormone level (>64 pg/ml, median, 51 pg/ml). 18 biopsies were available. Calcification was apparent on H&E in all cases and confirmed on 10 with von Kossa stains. All had calcification of small-medium caliber vessel walls. The calcification was predominantly stippled in 5, chunky in 2 cases and mixed stippled and chunky in 10. Calcification associated with thrombosis was seen in 11 and vessel wall necrosis in 4. Extravascular calcification was present in 10, involving subcutaneous tissue interstitium (7), perieccrine deposition (4), and dermis (1). Epidermal changes included full-thickness necrosis (3), ulceration (2), and erosion (1) to crust and vesicle formation (2). Dermal changes included reactive angioendotheliomatosis (4), perivascular chronic inflammation (4) and hemorrhage (2). Fat necrosis, present in 14, had septal fibrosis (3) and septal panniculitis (2) in a subset Conclusions: Nonuremic calciphylaxis is more common than recognized, accounting for >1/3 of our cases and disproportionately affects women. Obesity is the most common predisposing factor, but most patients had multiple comorbidities that could contribute to calciphylaxis.