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Few studies have assessed the overall importance of genetic factors on stroke risk, and the results have been contradictory. We used a large, population-based twin register and nationwide registries of death and hospitalization with long-term follow-up to estimate the effect of genetic factors on the risk of stroke.Through the population-based Danish Twin Register, we identified same-sex twin pairs born in 1870 through 1952 for whom at least 1 twin was recorded under a stroke diagnosis in the Register of Causes of Death or the Danish National Discharge Register. From the day of the first stroke event in each twin pair, the live co-twins were followed up for stroke. In survival analyses, we estimated the age- and sex-adjusted effect of zygosity on the risk of stroke death or hospitalization for stroke. Concordance rates, tetrachoric correlations, and heritability were also assessed.Thirty-five of 351 monozygotic pairs (10%) and 34 of 639 dizygotic pairs (5%) were concordant for stroke death. The age- and sex-adjusted relative risk of stroke death in monozygotic compared with dizygotic co-twins was 2.1 (95% CI, 1.3 to 3.3). The probandwise concordance rates were 0.18 (95% CI, 0.14 to 0.22) for monozygotic and 0.10 (95% CI, 0.08 to 0.13) for dizygotic pairs. Thirty-three of 309 monozygotic pairs (11%) and 39 of 560 dizygotic pairs (7%) were concordant for stroke hospitalization or stroke death. The age- and sex-adjusted relative risk of stroke hospitalization or stroke death in monozygotic compared with dizygotic co-twins was 1.5 (95% CI, 0.9 to 2.4). The probandwise concordance rates were 0.19 (95% CI, 0.15 to 0.24) for monozygotic and 0.13 (95% CI, 0.10 to 0.16) for dizygotic pairs. The heritability estimates were 0.32 for the liability to stroke death and 0.17 for the liability to stroke hospitalization or stroke death.The observed increased risk of stroke death and stroke hospitalization in monozygotic compared with dizygotic co-twins suggests that genetic factors increase the risk of stroke and that the size of this effect is moderate.