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Whereas greater physical activity (PA) is known to prevent cardiovascular disease (CVD), the relative importance of performing PA in sustained bouts of activity versus shorter bouts of activity on CVD risk is not known. The objective of this study was to investigate the relationship between moderate-to-vigorous PA (MVPA), measured in bouts ≥10 and <10 min, and CVD risk factors in a well-characterized community-based sample of white adults.We conducted a cross-sectional analysis of 2109 participants in the Third Generation Cohort of the Framingham Heart Study (mean age = 47 yr, 55% women) who underwent objective assessment of PA by accelerometry over 5–7 d. Total MVPA, MVPA done in bouts ≥10 min (MVPA10+), and MVPA done in bouts <10 min (MVPA<10) were calculated. MVPA exposures were related to individual CVD risk factors, including measures of adiposity and blood lipid and glucose levels, using linear and logistic regression.Total MVPA was significantly associated with higher HDL levels and with lower triglycerides, BMI, waist circumference, and Framingham risk score (P < 0.0001). MVPA<10 showed similar statistically significant associations with these CVD risk factors (P < 0.001). Compliance with national guidelines (≥150 min of total MVPA) was significantly related to lower BMI, triglycerides, Framingham risk score, waist circumference, higher HDL, and a lower prevalence of obesity and impaired fasting glucose (P < 0.001 for all).Our cross-sectional observations on a large middle-age community-based sample confirm a positive association of MVPA with a healthier CVD risk factor profile and indicate that accruing PA in bouts <10 min may favorably influence cardiometabolic risk. Additional investigations are warranted to confirm our findings.