Observational studies have shown that obesity considerably affects the cardiovascular system. Thus we conducted this Mendelian randomization (MR) analysis to evaluate the causal effect of childhood obesity on heart failure (HF) and its risk factors. We obtained genetic instruments from genome-wide association studies (GWAS) that investigated childhood obesity, HF, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), chronic kidney disease (CKD), valvular heart disease, myocarditis, hypertrophic cardiomyopathy, and hyperthyroidism. Inverse variance weighting (IVW), weighted median analysis, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were employed for MR analyses. In addition, the leave-one-out sensitivity test, MR-PRESSO global test, and Cochran's Q test were used for sensitivity analyses. Genetic evaluations showed that childhood obesity increases the risk of HF (odds ratio [OR] = 1.11, 95%CI: 1.05–1.17, p = 1.26 × 10−4), T2DM (OR = 1.17, 95%CI: 1.12–1.23, p = 8.80 × 10−12), AF (OR = 1.08, 95%CI: 1.05–1.12, p = 2.66 × 10−7), MI (OR = 1.08, 95%CI: 1.04–1.13, p = 3.35 × 10−4), and CAD (OR = 1.08, 95%CI: 1.03–1.13, p = 1.48 × 10−3). We found no association between childhood obesity and CKD, valvular heart disease, myocarditis, hypertrophic cardiomyopathy, or hyperthyroidism. Sensitivity analysis and Bonferroni's correction showed consistent results. Our study provides new evidence for the relationship between childhood obesity and HF and its risk factors. The results indicate that individuals with a history of childhood obesity require more clinical attention to prevent the development of HF. This study used two-sample Mendelian randomization analyses to demonstrate the causal associations between childhood obesity, and heart failure and its associated risk factors. • Childhood obesity increases the risk of heart failure (HF). • Childhood obesity increases the chance of developing some risk factors of HF. • Childhood obesity should be regarded as a novel risk factor in the prevention of HF. [ABSTRACT FROM AUTHOR]