Objectives Physical inactivity is a risk factor for cardiovascular disease (CVD). Cycling as a physical activity holds great potential to prevent CVD. We aimed to determine whether cycling reduces the risk of CVD and CVD risk factors and to investigate potential dose-response relationships.

Design Systematic review and meta-analysis of quantitative studies.

Eligibility criteria for selecting studies We searched four databases (Web of Science, MEDLINE, SPORTDiscus and Scopus). All quantitative studies, published until August 2017, were included when a general population was investigated, cycling was assessed either in total or as a transportation mode, and CVD incidence, mortality or risk factors were reported. Studies were excluded when they reported continuous outcomes or when cycling and walking were combined in them. We pooled adjusted relative risks (RR) and OR. Heterogeneity was investigated using I.

Results The search yielded 5174 studies; 21 studies which included 1,069,034 individuals. We found a significantly lower association in combined CVD incidence, mortality and physiological risk factors with total effect estimate 0.78 (95% CI (CI): 0.74–0.82; P<0.001; I²=58%). Separate analyses for CVD incidence, mortality and risk factors showed estimates of RR 0.84 (CI, 0.80 to 0.88; P<0.001; I²=29%), RR 0.83 (CI, 0.76 to 0.90; P<0.001; I²=0%), and OR 0.75 (CI, 0.69 to 0.82; P<0.001; I²=66%), respectively. We found no dose-response relationship or sex-specific difference.

Conclusions Any form of cycling seems to be associated with lower CVD risk, and thus, we recommend cycling as a health-enhancing physical activity.

Systematic review registration Prospero CRD42016052421.