Sugar-sweetened beverages (SSBs) are associated with increased cardiovascular disease (CVD). Whether this association holds for other important food sources of sugars is unclear. To address this question, we conducted a systematic review and meta-analysis of prospective cohort studies on the relationship of important food sources of fructose-containing sugars with CVD using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). MEDLINE, EMBASE, and Cochrane databases were searched through April 30, 2018. We included prospective cohort studies ≥1year reporting the relation of important food sources of fructose-containing sugars with CVD outcomes. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). Data were pooled using generic inverse variance method and expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of evidence was assessed using GRADE. Sixty-three prospective cohorts involving 3,375,264 participants and 123,575 events were included. Incident CVD was negatively associated with fruit (0.90 [0.86-0.94]), yogurt (0.84 [0.78-0.91]), and chocolate (0.74 [0.56-0.97]), while CVD mortality was positively associated with SSBs (1.20 [1.09-1.33]) and negatively associated with fruit (0.84 [0.77-0.92]) and breakfast cereals (0.76 [0.72-0.81]). Incident CHD was positively associated with SSBs (1.17 [1.08-1.26]) and negatively associated with fruit (0.87 [0.83-0.92]), breakfast cereals (0.80 [0.70-0.92]), and chocolate (0.88 [0.83-0.94]), while CHD mortality was only negatively associated with fruit (0.84 [0.76-0.94]), fruit juice (0.76 [0.64-0.91]), and breakfast cereal (0.69 [0.57-0.83]). Incident stroke was negatively associated with fruit (0.83 [0.78-0.89]), fruit juice (0.65 [0.51, 0.84), breakfast cereal (0.88 [0.80, 0.97]), and chocolate (0.85 [0.76-0.94]), and stroke mortality was negatively associated with fruit (0.82 [0.74-0.90]) and fruit juice (0.74 [0.62-0.87]). The overall certainty of the evidence by GRADE was strongest (“moderate”) for the associations of SSBs with CHD incidence and CVD mortality, chocolate with stroke incidence, and fruit with all outcomes; the remaining associations were graded as “very low” to “low”. Pooled analyses suggest that SSBs are associated with increased CVD while other important food sources of sugars, such as fruit, fruit juice, breakfast cereal, and chocolate, have neutral to protective associations. More research is needed to improve our confidence in these associations.