Background: Physical inactivity is an important cardiovascular risk factor. Aim: To investigate the association of physical inactivity with obesity, metabolic markers, type 2 diabetes mellitus, hypertension and metabolic syndrome in Chilean adults. Material and Methods: Participants from the National Health Survey 2009-10 (n = 5,157) were included in this study. Body mass index, waist circumference, metabolic markers (blood glucose, glycosylated hemoglobin and lipid profile) were the outcomes. Type 2 diabetes, hypertension and metabolic syndrome were determined using international criteria. Physical activity levels were determined using the Global Physical Activity Questionnaire and physical inactivity was defined as < 600 METs/minutes/week. Results: Compared to their physically active peers, inactive men and women had a higher odds ratio (OR) for obesity (OR: 1.77 [95% confidence intervals (CI): 1.29-2.42], p < 0.01 and 1.25 [95% CI: 102-1.54], p < 0.035, respectively), diabetes (OR: 2.47 [1.80-3.38], p < 0.01 and 1.72 [1.35-2.19], p = 0.002, respectively) and hypertension (OR: 1.66 [1.31-2.09], p < 0.01 and 1.83 [1.54-2.18] respectively. An association of physical inactivity with central obesity and metabolic syndrome was observed only in men (OR: 1.92 [1.42- 2.58], p < 0.01 and 1.74 [1.23-2.47], p < 0.01, respectively). Conclusions: Not meeting the physical activity recommendations is associated with obesity, diabetes, hypertension and metabolic syndrome, which are important cardiovascular risk factors.