Introduction: Health-compromising behaviours are often acquired in adolescence. Alongside broader public health interventions, preventive interventions within primary care have the potential to encourage long-lasting behaviour change by tailoring messages to each individual. The aim of this study is to determine the effectiveness of primary care interventions in reducing the 3 main cardiovascular risk behaviours (smoking, low physical activity and unhealthy diet) in adolescents aged 10–19 years. It is also to identify successful initiatives and ingredients for such success that could be replicated in primary care. Methods and analysis: This systematic review of the literature and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) recommendations. The following databases will be searched for articles published between January 1990 and December 2016: MEDLINE, EMBASE, PsychINFO, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, ISRCTN registry. Our search will focus on randomised and cluster randomised controlled trials of interventions conducted in primary care practices to reduce the 3 main cardiovascular risk behaviours in adolescents aged 10–19 years, compared with active (information leaflet, etc) or passive (usual care, etc) control conditions. The primary outcomes will be smoking, physical activity and diet, measured either objectively or by self-report. Secondary outcomes such as body mass index or insulin resistance will also be examined. 2 reviewers will independently screen articles, extract relevant data and assess study quality using the Cochrane risk of bias tool. A meta-analysis will be considered if the number of studies is sufficient and outcomes are sufficiently homogeneous. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria will be used to assess the quality of the evidence. Ethics and dissemination: This systematic review will add to our knowledge on the prevention of cardiovascular disease early in life and these findings will be disseminated through peer-reviewed publications and presentations at relevant conferences.