Primary prevention of childhood obesity and related hypertension is warrant given that both risk factors are intertwined and track into adulthood. This systematic review and meta-analysis assess the impact of school-based lifestyle interventions on children's body mass index (BMI) and blood pressure. We searched databases and prior reviews. Eligibility criteria were the following: randomized controlled trial design, evaluation of a school-based intervention, targeting children aged 4-12 years, reporting on BMI and/or related cardiovascular risk factors, reporting data on at least one follow-up moment. The effects on BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated by means of univariate and multivariate three-level random effects models. A total of 85 RCTs (91 papers) were included in the meta-analyses. In univariate models, the pooled effects were -0.072 (95%CI: -0.106; -0.038) for BMI, -0.183 (95%CI: -0.288; -0.078) for SBP and -0.071 (95%CI: -0.185; 0.044) for DBP. In multivariate analyses, the pooled effects of interventions were -0.054 (95%CI: -0.131; 0.022) for BMI, -0.182 (95%CI: -0.266; -0.098) for SBP and -0.144 (95%CI: -0.230; -0.057) for DBP. Parental involvement accentuated the beneficial effects of interventions. School-based lifestyle prevention interventions result in beneficial changes in children's BMI and blood pressure, and the effects on the latter may be stronger than and accrue independently from those in the former.