Purpose: Endothelial progenitor cells (EPCs) appear to interact with physical training. This study aimed to provide a comprehensive assessment of the relationship of moderate to vigorous physical activity (MVPA) with both angiogenic factors and EPC function in healthy children. Methods: Forty children (22 boys and 18 girls) aged 7 to 11 years participated in a 10-week MVPA program (duration: 45 min; intensity: 75%–85% of heart rate reserve; frequency: 4 sessions/wk). The anthropometric data, biochemical profile, EPCs number, EPCs colony-forming units, and vascular endothelial growth factor-A (VEGF-A) and nitric oxide (NO) plasma levels were evaluated before and after the MVPA program. Results: After a 10-week MVPA program, a significant increase was detected in circulating/functional capacity of EPCs, NO, and VEGF-A levels, associated with improvement of waist circumference and estimated maximum rate of oxygen consumption (VO2max). A strong positive correlation was found between delta of EPCs number and variation of both NO level (r = .677, P < .001) and VEGF-A level (r = .588, P < .001). Furthermore, a significant correlation between NO level variation and delta of VEGF-A level was observed (r = .708, P < .001). Conclusion: Our findings suggest that lifestyle intervention implemented by MVPA program can contribute meaningfully to improve circulating/functional capacity of EPCs in healthy children, possibly due to the increase of plasma NO and VEGF-A levels.