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This study estimated the biopsychosocial factors related to active physical behavior in the Brazilian population with and without chronic non-transmissible disease (NCD). Cross-sectional study of the National Health Survey (NHS) in Brazil, with 60,202 individuals in 2013. Participants were randomly selected by complex sampling. The outcome was physically active behavior measured by performing a minimum of 150 min of physical exercise per week. The independent variables were social and psychological characteristics, lifestyle and health. Cox regression was applied to estimate the prevalence ratio (PR). There are 29,666 (48.3%; 95% CI 47.0–50.0) participants reported having NCD. Not being a smoker or alcoholic, living in an urban area (PR = 1.44; CI95% 1.23–1.68/PR = 1.38; CI95% 1.08–1.75), having informal social support (PR = 1.26; CI95% 1.10–1.44/PR = 1.19; CI95% 1.05–1.34), A social class (PR = 0.43; CI95% 0.25–0.73/PR = 0.46; CI95% 0.26–0.80), high schooling (PR = 0.34; CI95% 0.23–0.51/PR = 0.33; CI95% 0.24–0.46) as well as paid work (PR = 0.87; CI95% 0.78–0.96/PR = 0.89; CI95% 0.79–0.99) are more associated with active lifestyle in both groups. However, only in the group without NCD, the male sex (PR = 1.42; CI95% 1.28–1.57), no having some disability (PR = 1.31; CI95% 1.03–1.66) and having private health insurance (PR = 1.26; CI95% 1.13–1.41) were more associated with active behavior, while in the group with NCD, being elderly (PR = 1.22; CI95% 1.05–1.42), not be white (PR = 0.85; CI95% 0.77–0.95) and not having restful sleep (PR = 1.23; CI95% 1.08–1.40) are associated with active lifestyle. People with and without NCD in Brazil have very close active behavior, however, some biopsychosocial factors such as: sex, age, lifestyle, socioeconomic level are unevenly associated with the active lifestyle in the groups. Thus, therapeutic or preventive proposals as well as public policies for health promotion must observe these distinctions when elaborating their actions.