The molecular epidemiology of stroke is critically lacking in the developing world. We explored the relationships between genetics polymorphism and risk for ischemic stroke among the residents of Casablanca, Morocco. Ninety-one stroke patients matched 1:2 for their age, gender, and ethnic background to 182 healthy controls who were genotyped for the prothrombin G20210A mutation and factor V (FV) Leiden and were assessed for conventional risk factors for stroke. No significant association was found between prothrombin gene mutation with stroke (p = .054). Regarding stroke subtypes, significant relationships between patients with a large artery disease subtype of stroke and this mutation was found compared to controls (p = .046). As a genetic risk factor to develop this event, a strong association was observed when adjusted for conventional vascular risk factors (adjusted OR, 4.3; p = .029). No FV Leiden was found. We suggest that prothrombin mutation but not FV Leiden should be considered as a modest genetic risk factor for large artery disease stroke subtype in the Moroccan population.