Background:This trial aimed to determine the impact of high risk approach for primary prevention of cardiovascular diseases (CVD) in children of families at high risk for premature CVD. Methods:This trial was conducted as part of the Isfahan Healthy Heart Program, and comprised 105 adolescents, aged 12-18 years, whose parents were admitted because of premature CVD (< 55 years) to the hospitals affiliated to Isfahan University of Medical Sciences. After physical examination, filling in questionnaires and blood sampling, oral and written information about healthy lifestyle especially for healthy nutrition, increasing physical activity and tobacco control were provided for children and their families. All assessments were repeated after one year. Findings:The mean value of all anthropometric indexes including weight, height, waist and hip circumferences as well as systolic and diastolic blood pressure and biochemical factors showed significant changes (P < 0.01) after intervention. The mean body mass index decreased from 21.03 ± 3.8 to 20.99 ± 3.9 kg/m2. Serum triglycerides decreased from 100.31 ± 41.4 to 95.48 ± 40.6 mg/dl, total cholesterol decreased from 164.51 ± 27.2 mg/dl to 158.44 ± 30.5 and LDL-cholesterol from 99.37 ± 23.5 to 93 ± 24.9 mg/dl. HDL-cholesterol increased from 44.16 ± 8.6 to 46.34 ± 10.5 mg/dl. Changes in blood sugar and lipid profile was more favorable in boys than in girls, for instance total cholesterol decreased from 165.5 ± 30.6 to 157.46 ± 31.4 mg/dl in boys and 163.47 ± 23.2 to 159.47 ± 29.8 mg/dl in girls, respectively. Conclusion:In spite of the existing genetic tendency for CVD and its risk factors, education of healthy lifestyle can be effective in controlling CVD risk factors. This high risk approach had favorable results and should be considered in addition to the treatment of the CVD patients. Key words: Premature cardiovascular disease, Family history, Lifestyle, Prevention.