In this paper, we focus on the importance of interaction between adverse genetic mutations, and clinical risk factors in the development of ischemic stroke, knowing that this disease is multifactorial common that is affected by a number genetic mutations and environmental factors. The apolipoprotein E4 allele (APO e4), Factor II G20210A prothrombin (blood clotting protein), and Factor V genotypes were examined in 165 patients with ischemic Stroke group and 165 Control group, at the Laboratory of Human Genetics and Molecular Pathology, University Hassan II- Faculty of Medicine in Casablanca and the department of neurology at the campus teaching hospital of Casablanca and Rabat. Logistics regression models and bivariate correlation analysis with Karl Pearson's method were used to estimate the role of co-occurrences of the clinical risk factors and genetic mutations in ischemic stroke. The presence of the APO e4 is dominant in Stroke group than Control group and its association with hypertension, smoking and cholesterol increases the risk of ischemic stroke. FV mutation in association with hypertension or diabetes mellitus reveals a strong correlation in ischemic stroke. We found no significant relationship between the ACE D / D, FII, MTHFR 677TT genotype and clinical factors. In some combinations, pairing of adverse genetic factors, which alone confer non-significant risk, with clinical risk factors can greatly increase the risk of having an ischemic stroke.