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Nitrous oxide (N2O) is increasingly used as a recreational drug, and is presumed relatively safe and innocent. The risks for neurological complications are often known, however the risks of serious thromboembolic events are not. We describe three cases of acute thromboembolic events resulting in serious cardiovascular complications after N2O abuse: one case of myocardial infarction that resulted in a reduced ejection fraction, one case of peripheral arterial occlusion that led to limb amputation and one case of pulmonary embolism that resulted in hemodynamic instability requiring extracorporeal membrane oxygenation (ECMO) and surgical removal. All patients were young adults with a low cardiovascular risk profile. N2O inactivates vitamin B12, leading to vitamin B12 deficiency and subsequent to hyperhomocysteinemia, which is associated with the formation of fibrinolysis-resistant blood thrombi. In conclusion, we contest the safety and innocence of recreational N2O (ab)use. Our three cases illustrate that, next to previously described neurological complications, the use of nitrous oxide is associated with thromboembolic cardiovascular complications, presumably mediated by hyperhomocysteinemia.