Introduction: There are no published data in relation to this topic at population level from the Southern Cone of Latin America. Hence, we assessed the hypothesis that higher levels of occupational PA will be associated with lower plasma levels of lipoproteins, apolipoproteins, C reactive protein, blood pressure and lower body mass index (BMI) compared to those of the subjects who performed sedentary activities at work Methods: The CESCAS I study is a population-based prospective cohort study with a 4-stage stratified sampling of a general population from four mid-sized cities in Argentina, Chile and Uruguay. PA was assessed using the International Physical Activity Questionnaire long form. We expressed the total PA score per week as total metabolic equivalent per minutes per week. To test univariate associations between tertiles (T) of occupational PA and continuous variables we used simple linear regression models and chi-square test for categorical variables. The changes in crude and adjusted means of systolic and diastolic blood pressure, BMI, lipoproteins, C reactive protein and apolipoproteins AI and B were tested using multivariate linear regression models Results: The working population consisted in 1,868 men and 1,672 women. In men, T3 compared to T1 (reference category) showed lower prevalence of university education (12.4% vs. 26.9 %; p 0.001 (90 and 235 of 1,868, respectively)), obesity or overweight (76.0% vs. 82.9 %; p 0.001 (553 and 724 of 1,868, respectively)) and higher prevalence of active transportation (60.2 vs. 51.9%; p 0.002 (453 and 439 of 1,868, respectively)). In multivariate analysis, T2 vs. T1 showed a reduction of BMI (mean adjusted difference -1.0; p 0.001), systolic blood pressure (-2.5 mmHg; p 0.027), glycemia (-3.9 mg/dL; p 0.024), triglycerides (-32.0 mg/dL; p 0.003) and higher mean values of high density lipoprotein (HDL) (2.5 mg/dL; p 0.002) and apolipoprotein AI (13.7 mg/dL; p 0.002). When compared, T3 vs. T1 only showed lower mean values of BMI and triglycerides and higher values of HDL but with a lower magnitude. In women, T3 compared to T1 showed lower prevalence of university education (20.4 vs. 29.5%; p 0.001), lower sleep hours (7.4 vs. 7.7; p 0.007) and higher prevalence of major depressive episode (16.9 vs. 11.5; p 0.003). In multivariate analysis, T3 compared to T1 showed higher levels of HDL (mean adjusted difference 2.0 mg/dL; p 0.025) Conclusions: Moderate or high physical activity at work was not associated with an increased cardiovascular risk profile. On the contrary, the results showed that this population would have a lower cardiovascular risk, especially in those who perform moderate intensity activities compared to those performing sedentary activities. The lack of associations in woman could be related to a better baseline risk profile and the higher prevalence of active transportation in all categories of occupational PA compared to men