Factor V Leiden is a well-recognized etiology of venous thrombosis, but reports of stroke in patients with this mutation are few. Marijuana smoking has rarely been associated with thrombosis of cerebral and renal arteries and may be due to a direct toxic effect on the endothelium. Reported here is the case of a previously healthy young man who smoked marijuana on a daily basis and had an occipital lobe stroke; he was found to be heterozygous for factor V Leiden. This case suggests that marijuana smoking may increase the risk of arterial thrombosis in otherwise healthy individuals who are heterozygous for factor V Leiden.