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Nitrous oxide is a commonly used inhaled anesthetic for medical procedures, as well as a drug of abuse throughout the world. Excessive nitrous oxide inhalation has been shown to cause a functional vitamin B12 deficiency and hyperhomocysteinemia, which can lead to peripheral neuropathy and hypercoagulability, respectively. While the development of neurologic toxicity from chronic nitrous oxide abuse (i.e., encephalopathy, myelopathy, and neuropathy) has been previously described, the thrombotic potential of chronic nitrous oxide abuse is less known. The authors report two cases of nitrous oxide abuse leading to both neurologic and thrombotic complications.