Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), LILACS (Latin American and Caribbean Health Sciences), CNKI (China National Knowledge Infrastructure), Wanfang (China) and the South African Department of Health databases were searched. In addition the archives at the WHO Collaborating Centre for Nutrition and Oral Health at Newcastle University and reference lists of reviews were searched and experts contacted for further relevant papers Study selection Intervention, cohort population or cross sectional studies were considered where there was any intervention to alter the intake of sugar or the intake of sugars or change of sugar intake was monitored. The main outcome was caries incidence. The GRADE (Grading of Recommendations Assessment Development and Evaluation) system was used to assess study quality. Data extraction and synthesis Separate data abstraction forms were designed for RCTs and observational studies and meta-analyses were to be conducted where possible. Results Sixty-five papers reporting 55 studies were included. No RCTs were identified. Three studies (four papers) were interventional, eight (12 papers) were prospective cohort, 20 (25 papers) were population based and 24 (25 papers) were cross-sectional. Data variability limited meta-analysis. Of the studies, 42 out of 50 of those in children and five out of five in adults reported at least one positive association between sugars and caries.Five of the eight cohort studies allowed comparison of dental caries development when sugars consumption was equivalent to a level < 10% E (Energy) or > 10% E. All eight studies found higher caries with sugars intake > 10% E compared with < 10% E. Conclusions This in-depth systematic review shows consistent evidence of moderate quality supporting a relationship between the amount of sugars consumed and dental caries development. There is evidence of moderate quality to show that dental caries is lower when free-sugars intake is < 10% E. Dental caries progresses with age, and the effects of sugars on the dentition are lifelong. Even low levels of caries in childhood are of significance to levels of caries throughout the life course. Analysis of the data suggests that there may be benefit in limiting sugars to < 5% E to minimise the risk of dental caries throughout the life course.