This study sought to determine the effectiveness of multiple risk factor interventions aimed at modifying major cardiovascular risk factors for the primary prevention of cardiovascular disease in low- and middle-income countries (LMIC). We searched electronic databases for randomized controlled trials of health promotion interventions to achieve behavior change. The pooled effect indicated a reduction in systolic blood pressure (-6.72 mm Hg; 95% confidence interval [CI]: -9.82 to -3.61; I2 = 91%), diastolic blood pressure (-4.40 mm Hg; 95% CI: -6.47 to -2.34; I2 = 92%), body mass index (-0.76 kg/m2; 95% CI: -1.29 to -0.22; I2 = 80%), and waist circumference (-3.31 cm; 95% CI: -4.77 to -1.86; I2 = 55%) in favor of multiple risk factor interventions. There is some evidence that multiple risk factor interventions may lower blood pressure levels and anthropometrics in populations in LMIC settings at high risk of hypertension and diabetes.