Obesity has been confirmed to be associated with cardiovascular disease, but previous studies have focused on adults, and whether childhood obesity is associated with cardiovascular disease in adulthood needs further research.This Mendelian randomization (MR) study aimed to investigate the associations of childhood and adult body mass index (BMI) with the risk of chronic heart failure (CHF) and ischemic stroke (IS).Independent genetic instruments, demonstrating a strong association with exposure at the genome-wide significance level (P < 5 × 10-8), were carefully selected from comprehensive genome-wide association studies conducted within relevant European populations. Summary-level data for CHF and IS were obtained from the EBI database and large consortia of European population. To enhance robustness and generalizability, the analysis was replicated in an East Asian population cohort.According to a MR analysis based on a European population, a higher adult BMI was associated with an increased risk of CHF [(odds ratio (OR) 1.594, 95% confidence interval (CI) 1.483-1.713)] and IS (OR 1.163, 95%CI 1.096-1.233). In addition, higher childhood BMI level was associated with a higher risk of CHF (OR 1.323, 95%CI 1.153-1.524).and the effect was mainly driven by adult BMI. Replication analyses of adult BMI in East Asian populations showed consistent findings that adult BMI was associated with the risk of CHF (OR 2.167, 95%CI 1.786-2.630) and IS (OR 1.259, 95%CI 1.128-1.406).Our study findings provide compelling evidence for the significant influence of adult BMI on the occurrence of CHF and IS. Furthermore, our observations suggest that the positive association between childhood BMI and the risk of CHF in adulthood can largely be attributed to individuals who maintain obesity into later life.© 2024 The Authors. Published by Elsevier B.V.