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A 22-year-old man was referred for orthopedic follow-up after an ankle injury. Initial evaluation in urgent care included radiographs with negative findings. After a delayed presentation, a course of functional treatment was recommended. Subsequently, he developed a deep venous thrombosis and pulmonary emboli. He was found to be factor V Leiden deficient and was fully anticoagulated on warfarin. Later reevaluation revealed a steppage gait and foot drop. Electrodiagnostic studies (ie, electromyography and nerve conduction studies) revealed a severe peripheral polyneuropathy. The patient admitted to engaging in high-volume recreational use of nitrous oxide. Neurological evaluation confirmed vitamin B12 deficiency consistent with the toxic effects of nitrous oxide. The patient's condition improved with vitamin B supplementation, bracing, and avoidance of nitrous oxide and similar neurotoxins. He participated in a 3-month physical rehabilitation program, and he displayed partial recovery at most recent follow-up. [Orthopedics. 2018; 41(3):e432-e433.].