Objective: To investigate the cumulative effect of family history of cardiovascular disease(CVD)and overweight on ischemic stroke events in the Mongolian population. Methods: Study participants were recruited from 32 villages from May 2002 to August 2012 in Kezuohou Banner(county)and Naiman Banner in Inner Mongolia, China. Among 3 457 Mongolian people aged ≥20 years old living in these villages, 2 589 were selected to participate in this study. None of the participants had chronic kidney disease, malignant tumor, thyroid disease or adrenalopathy, or acute infectious disease. The 2 589 participants were followed for a mean of 9.2 years. Six participants were lost to follow up, resulting in a follow-up rate of 99.8%. Information collected included demographic characteristics, lifestyle risk factors, alcohol consumption, cigarette smoking, history of disease, family history of CVD, and physical examination. Ischemic stroke incidence information was collected during follow-up. All participants were categorized into four subgroups according to family history of CVD and overweight status. Cox proportional hazards models were used to estimate the hazard ratios(HR)and 95% CI of ischemic stroke events among subgroups, compared with the subgroup with no family history of CVD and body mass index(BMI)<24 kg/m2(the reference group). Results: Among 2 589 participants, 76 ischemic stroke events occurred after follow-up, and 8 were excluded because of lack of key data. Finally, 2 581 participants were included in the analysis, and the incidence density was 323/100 000 person-years. The cumulative incidence rates of ischemic stroke were 2.48%, 1.86%, 6.67% and 9.00% in the no family history of CVD and BMI <24 kg/m2, no family history of CVD and BMI ≥24 kg/m2, family history of CVD and BMI <24 kg/m2 and family history of CVD and BMI ≥ 24 kg/m2 subgroups, respectively. Using the Cox proportional hazards model, after further adjustment for age, gender, smoking, drinking, FPG, hypertension, total cholesterol, triglycerides, and heart rate, the risk of ischemic stroke in the subgroup with a family history of CVD and BMI ≥24 kg/m2 was higher than the reference group(HR: 2.61, 95% CI: 1.16-5.87). However, the risk of ischemic stroke in other two groups was not statistically significant compared with the reference group. The HR(95% CI)values in the no family history of CVD and BMI ≥24 kg/m2and family history of CVD and BMI <24 kg/m2 subgroups were 1.18(0.5- 2.39)and 1.27(0.67- 2.42), respectively. Conclusion: In the Mongolian population, a family history of CVD and coexistent overweight may increase the risk of ischemic stroke events, suggesting that in people with family history of cardiovascular disease, weight control is conducive to the prevention of ischemic stroke.