Data sources Medline, Embase, CINAHL and PubMed.Study selection Studies published in peer-reviewed journals focusing on dental caries of primary teeth and risk and/or protective factors, in healthy children aged equal to or less than six years, including randomised controlled trials (RCTs) with an intervention period of at least one year for caries, other intervention studies, and observational studies (such as cohort, case-control, ecologic and cross-sectional studies); risk and/or protective factors included: breastfeeding beyond one year of age, breastfeeding beyond two years of age, consumption of liquids that contain free sugars from an infant feeding bottle, consumption of complementary drinks that contain free sugars, consumption of complementary foods that contain free sugars, oral hygiene provided by a parent/caregiver, oral health education for caregivers, water with an optimum concentration of fluoride, consumption of fluoridated milk and salt fluoridation.Data extraction and synthesis Five reviewers independently screened the title and abstract of the identified citations and 5% of them were screened by all reviewers. Data extraction was undertaken by two reviewers. The evidence was classified into 12 groups in accordance with the 12 review questions. Eligible studies were synthesised and meta-analysis performed where appropriate. Risk of bias was tested by the Cochrane 'risk of bias' tool for RCTs and the ROBINS-I for non-randomised trials. The quality of evidence related to each of the 12 review questions was assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).Results After initial search of 13,831 studies, 137 eligible studies were included in the systematic review and grouped into 10 out of 12 review questions (no eligible study was identified for two review questions). Among those ten review questions, only two review questions had RCTs to address the answers; others were answered by observational studies and/or quasi-experimental studies. A prospective cohort study displayed no significant difference was found in severity of caries among five-year-old children inbetween those breastfed for nearly 23 months and those breastfed up to one year. Observational studies showed increased risk of early childhood caries (ECC) was associated with consumption of sugar in both bottles and complementary foods. Results of meta-analysis of three RCTs stated that children of caregivers who received oral health education had lower chance of having ECC than those who had never received oral health education (OR 0.39, 95% CI 0.19 to 0.79, P = 0.009). Another result from meta-analysis demonstrated that lower pooled mean dmft was found in children living in areas with fluoridated water than those who lived in non-fluoridated areas (-1.25, 95% CI -2.14 to -0.36, P = 0.016). Children who consumed fluoridated milk and fluoridated salt reduced the risk of ECC compared to those who did not. No publication bias was observed in the meta-analysis.Conclusions Evidence with moderate quality demonstrated that children with access to fluoridated water and fluoridated supplements could lower their risk of ECC; children with caregivers who had received oral health education had lower levels of ECC. Evidence with low quality suggested that breastfeeding up to two years old did not increase the risk of ECC; consumed sugars in bottles and complementary foods increased the risk of ECC.