To determine the association of total and added fructose-containing sugars on cardiovascular (CVD) incidence and mortality.MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled.Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P<.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types.Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. REGISTRATION: clinicaltrials.gov, NCT01608620.