Objective: Although a variety of potential inherited and acquired aetiologies have been defined as a risk factor for ischemic stroke (IS) in paediatric patients, we aimed to revisit the influence of prothrombin G20210A (PT), methylenetetrahydrofolate reductase C677T (MTHFR-C677T) and hyperhomocysteinemia on the initial stroke episode. Material and Methods: This retrospective cross-sectional survey was conducted between 2003-2004. Paediatric patients who had been admitted and/or followed up with the diagnosis of IS constituted the patient group (Group I). Nineteen children who were followed up in the healthy children policlinics were elected for control group (Group II). Thrombophilic gene mutation analysis was performed through enzymatic polymerase chain reaction. The homocysteine level was quantified through a chemical immunoassay method. Results: There was no significant difference between the groups in terms of age [10 (1-18), p=0.98], gender (p=1.0), and ethnicity (p=0.27). The family history of IS that suggested hereditary thrombophilia was significantly higher in Group I (p<0.001). Additionally, it showed a 2,38 times greater risk of ischemic stroke. The rate of neither PT (p=1.0) nor MTHFR-C677T (p=0.19) were considerably higher in group I. While homocysteine level was higher in group I (12,6 versus 7.5 µmol/L, p=0.014), the rate of hyperhomocysteinemia was near-significant (p=0.09). In multi-variate analysis, none of the variables revealed a significant impact on the IS. Conclusion: Limited number of patient count was the major limitation of the current study. The coexistence of clinical and genetic factors seems to be more determinant than that of a genetic mutation per se.