The aim of this study was to evaluate associations between body-weight fluctuation and risk of mortality and cardiovascular diseases (CVD). PubMed, EMBASE databases and Cochrane Library were searched for cohort studies published up to May 20, 2019, reporting on associations of body-weight fluctuation and mortality from all causes, CVD and cancer, as well as morbidity of CVD and hypertension. Summary relative risks (RRs) were estimated using a random-effects model. Twenty-five eligible publications from 23 studies with 441,199 participants were included. Body-weight fluctuation was associated with increased risk for all-cause mortality (RR, 1.41; 95% confidence interval (CI): 1.27-1.57), CVD mortality (RR, 1.36; 95% CI 1.22-1.52), and morbidity of CVD (RR, 1.49, 95% CI 1.26-1.76) and hypertension (RR, 1.35, 95% CI 1.14-1.61). However, there was no significant association between weight fluctuation and cancer mortality (RR, 1.01; 95% CI 0.90-1.13). No evidence of publication bias was observed (all > 0.05) except for studies on all-cause mortality (Egger's test, = 0.001; Begg's test, = 0.014). Body-weight fluctuation was associated with higher mortality due to all causes and CVD and a higher morbidity of CVD and hypertension.