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Intro/purpose: Childhood obesity is strongly associated with the pathophysiology of various diseases, including cardiovascular disease (CVD). It is necessary to combat the unfavorable outcomes of obesity at a young age by utilizing effective interventions, such as exercise programs. Therefore, we sought to examine the effects of a jump rope exercise program on CVD risk factors, including body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls. Methods: Forty girls (age 14-16) were recruited and randomly assigned to either a jump rope exercise group (EX, n = 20) or control group (CON, n = 20). The EX group exercised 5 days/week. Body composition, nitrate and nitrite levels, endothelin-1 (ET-1), c-reactive protein (CRP), blood pressure, and arterial stiffness were measured before and after 12 weeks. Results: There were significant group by time interactions following the 12-week jump rope exercise program. Body composition, central adiposity, blood pressure, and brachial-to-ankle pulse wave velocity, an indicator of arterial stiffness (baPWV), all significantly decreased (P < 0.05) after 12 weeks. Nitrate and nitrite levels increased significantly (P < 0.05) along with a significant reduction in CRP levels (P < 0.05). There were no significant changes in ET-1 (P = 0.22). Conclusion: These findings indicate that jump rope exercise may be an effective non-pharmacological intervention to improve body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls. Jumping rope is an easily accessible and enjoyable exercise modality that may have important health implications for the prevention of CVD and other metabolic diseases at an early age.