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Abstract Background The recreational use of nitrous oxide is becoming increasingly common among teenagers and young adults. Since 2018, the use of nitrous oxide has increased exponentially and has become a public health problem. Case presentation A 23-year-old patient was referred to accident and emergency (A&E) by his general practitioner for deterioration in general condition, vomiting, diarrhea and febrile headache at 39 °C. He reported that he had been partying for a month and consuming alcohol, cannabis and nitrous oxide. Three days before the consultation, he reported increased abdominal pain in the right iliac fossa. His homocysteine concentration was 51.9 μmol/L, and his plasma methyl malonate concentration increased to 4.45 μmol/L. A thoracic and abdominal CT scan revealed right iliac venous thrombosis associated with bilateral pulmonary embolism. Conclusion Nitrous oxide inhibits the activity of methionine synthetase. We therefore observed an increase in plasma homocysteine and 5-methyl-THF. The increase in homocysteine could be responsible for the pro-thrombotic activity resulting from nitrous oxide intoxication. At present, no threshold or duration of exposure has been identified as being particularly likely to cause complications. It is likely that other factors coexist, such as coagulation disorders and polymorphisms of the MHTFR gene, which can lead to hyperhomocysteinaemia, cannabis consumption, inflammatory conditions and others. Treatment is based on vitamin B12 supplementation and curative anticoagulation. Some authors also recommend folate supplementation. Consumption of nitrous oxide could be associated with arterial and venous thromboembolic disease.