BACKGROUND: Little is known about the degrees and shapes of associations of changes in obesity indices with cardiovascular disease (CVD) and mortality risks. We aimed to conduct a dose-response meta-analysis for the associations of changes in weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and waist-to-height ratio with CVD events, CVD-specific deaths, and all-cause mortality. METHODS: We searched MEDLINE via OvidSP, Embase via OvidSP, Web of Science, CINAHL, and Scopus for articles published before January 8, 2023. Dose-response relationships were modeled using the one-stage mixed-effects meta-analysis. Random-effects models were used to pool the relative risk (RR) and 95% confidence interval (CI). RESULTS: We included 122 articles. Weight change was negatively associated with deaths from CVD and any cause, while WC change elevated CVD-specific mortality. Non-linear relationships also confirmed the adverse effects of increased WC on CVD-specific mortality. Additionally, gains of 5 kg in weight and 1 kg/m in BMI or more were associated with elevated CVD events, especially among young adults and individuals without CVD. Conversely, reductions of 5 kg in weight and 1 kg/m in BMI or more were associated with higher CVD-specific and all-cause deaths than increased counterparts, particularly among old adults and individuals with CVD. Similar non-linear relationships between relative changes in weight and BMI and deaths from CVD and any cause were observed. CONCLUSIONS: The effects of changes in weight and BMI on CVD outcomes were affected by age and cardiovascular health. Tailored weight management and avoidance of increased WC should be recommended.