BACKGROUND: Studies on the impact of counterfactual scenarios of physical activity on premature deaths from non-communicable diseases (NCDs) are sparse in the literature. We estimated preventable premature deaths from NCDs (diabetes, ischemic heart disease, stroke, and breast and colon cancers) in Brazil by increasing population-wide physical activity (i) to theoretical minimum risk exposure levels; (ii) reaching the physical activity recommendation; (iii) reducing insufficient physical activity by 10%; and (iv) eliminating the gender differences in physical activity. METHODS: Preventable fractions were estimated using data from a nationally representative survey, relative risks from a meta-analysis and number of premature deaths (30-69 years) from the Brazilian Mortality Information System. RESULTS: Physical activity could potentially avoid up to 16 700 premature deaths from NCDs in Brazil, corresponding to 5.75 and 3.23% of premature deaths from major NCDs and of all-causes, respectively. Other scenarios suggested the following impact on premature deaths: reaching physical activity recommendation (5000 or 1.74% of major NCDs); 10% reduction in insufficient physical activity (500 or 0.17% of major NCDs); eliminating gender differences in physical activity (1000 or 0.33% of major NCDs). CONCLUSIONS: Physical activity may play an important role to reduce premature deaths from NCD in Brazil.