Objective Sugars‐sweetened beverages are associated with increased risk of cardiovascular disease (CVD). To assess whether this association holds for the fructose‐containing sugars they contain, we conducted a systematic review and meta‐analysis of prospective cohort studies. Methods MEDLINE, EMBASE and Cochrane Library (through October 31, 2016) were searched for relevant studies. We included prospective cohort studies investigating the association between fructose‐containing sugars (total sugars, fructose, sucrose and added sugars) and incident CVD. Two independent reviewers reviewed and extracted the relevant data and assessed study quality (Newcastle‐Ottawa Scale). Risk estimates of extreme comparisons (lowest versus highest quantile) were pooled using inverse variance random effects models and expressed as risk ratios (RR) with 95% confidence intervals (95% CI). Inter‐study heterogeneity was assessed with Cochran Q statistic and quantified with the I 2 statistic. The overall quality of the evidence was assessed using the Grading of recommendations assessment, development, and evaluation (GRADE). Results The eligibility criteria were met by 7 prospective cohort studies (10 cohort comparisons) involving 530,268 individuals and 15,657 incident cases of CVD observed over an average follow‐up of 11.2 years. Total sugars (RR, 1.07 [95% CI, 1.01 to 1.13]) and fructose (RR, 1.08 [95% CI, 1.01 to 1.15]) but not sucrose (RR, 0.97 [95% CI, 0.88 to 1.07]) or added sugars (RR, 1.03 [95% CI, 0.85 to 1.24]) were associated with increased incidence of CVD. There was no evidence of heterogeneity in any of the analyses except for added sugars which showed evidence of substantial heterogeneity (I 2 =82%, P=0.004). The overall quality of the evidence was graded as “very low quality” for all associations owing to a downgrade for serious imprecision for total sugars, fructose, and sucrose and separate downgrades for serious imprecision and serious inconsistency for added sugars. Conclusions Current evidence does not allow us to conclude with certainty that all fructose‐containing sugars are associated with increased risk of CVD owing to the very low quality of evidence and the inconsistency across types of sugars. Further research should confirm whether the adverse association seen between sugars‐sweetened beverages and CVD applies to other important food sources of sugars. Protocol registration: clinicaltrials.gov identifier, NCT01608620 Support or Funding Information Canadian Diabetes Association, Canadian Institutes of Health Research, Banting and Best Diabetes Centre and PSI Foundation