The aim of this study was to identify hereditary and acquired risk-factors as they are related to the occurrence of stroke in children. We identified 21 children with stroke. A search of the Factor V Leiden mutation, the Factor II G20210A variant, and the thermolabile variant of methylenetetrahydrofolate reductase was performed in patients and in a control group (n = 115). We identified risk factors of acquired and/or hereditary nature for stroke in 19 of 21 children. Eleven children had three or more risk factors, seven had two risk factors, and one child had only one risk factor. We found three carriers (14.3%) of the Factor V Leiden mutation, two carriers (9.5%) of the Factor II G20210A variant, eleven (52.4%) thermolabile variant of methylenetetrahydrofolate reductase heterozygote carriers, and one (4.8%) homozygotes for this variant. Frequencies of the Factor V Leiden mutation and the Factor II variant were higher in patients than in controls, suggesting that these variants are associated with an increased risk of stroke in childhood. Homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase was equally frequent amongst patients and controls. Our study confirms that stroke in children is commonly associated with a combination of multiple risk factors, both genetic and acquired, and that the Factor V Leiden mutation and the Factor II G20210A variant are predisposing factors for this situation.