OBJECTIVE: This study aims to compare adolescents' cardiometabolic risk score through an integrative classification of physical activity (PA), which involves the combination of moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB). METHODS: A cross-sectional study derived from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study database (2006-2008) was conducted in adolescents (  = 548; boys, 47.3%; 14.7 ± 1.2 years) from 10 European cities. MVPA and SB were objectively measured using accelerometry. Adolescents were divided into 4 categories according to MVPA (meeting or not meeting the international recommendations) and the median of SB time (above or below sex- and age-specific median) as follows: High-SB & Inactive, Low-SB & Inactive, High-SB & Active, and Low-SB & Active. A clustered cardiometabolic risk score was computed using the homeostatic model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol, sum 4 skinfolds, and cardiorespiratory fitness (CRF). Analyses of covariance were performed to discern differences on cardiometabolic risk scores among PA categories and each health component. RESULTS: The cardiometabolic risk score was lower in adolescents meeting the MVPA recommendation and with less time spent in SB in comparison to the high-SB & Inactive group ( < 0.05). However, no difference in cardiometabolic risk score was established between High-SB or Low-SB groups in inactive adolescents. It is important to note that CRF was the only variable that showed a significant modification (higher) when children were compared from the category of physically inactive with "active" but not from high- to low-SB. CONCLUSIONS: Being physically active is the most significant and protective outcome in adolescents to reduce cardiometabolic risk. Lower SB does not exhibit a significant and extra beneficial difference.