A 43-year-old woman with a history of cocaine abuse presented with decreased mental responsiveness and cyanosis of the extremities several hours after repeated use of "crack" cocaine. She developed bilateral hand compartment syndrome requiring emergency fasciotomy and gangrene of both hands and legs despite anticoagulant and antithrombotic therapy. Digital and above-knee amputations were performed. There was no evidence of an autoimmune disorder or vasculitis on laboratory evaluation and tissue histology. Peripheral vasospasm may have been the mechanism of toxicity in this case, and the use of intravenous vasodilators should be considered as potential additional therapy.