Adolescence is associated with behavioral changes offering opportunities for prevention of cardiovascular risk behaviors. Primary care physicians are ideally placed to deliver preventive interventions to adolescents. The objective was to systematically review the evidence about effectiveness of primary care-led interventions addressing the main cardiovascular risk behaviors in adolescents: physical activity, sedentary behaviors, diet and smoking. PubMed, Embase, PsycINFO, CINAHL, Cochrane, ClinicalTrials.gov, and ISRCTN registry were searched from January 1990 to April 2020. Randomized controlled trials of interventions in primary care contexts on at least one of the cardiovascular behaviors were included, targeting 10–19-year old adolescents, according to the World Health Organization's definition. Two authors independently assessed risk of bias. Twenty-two papers were included in the narrative synthesis, reporting on 18 different studies. Interventions targeting smoking uptake seemed more effective than interventions targeting established smoking or the three other risk behaviors. Intervention components or intensity were not clearly associated with effectiveness. Risk of bias was mostly unclear for most studies. There is little evidence for specific interventions on adolescents' cardiovascular risk behaviors in primary care, mainly due to studies' methodological limitations. Further research should investigate the effectiveness of opportunistic primary care-based interventions as compared to more complex interventions, and address the methodological shortcomings identified in this review.