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Accumulating evidence suggests that the built environment may be associated with cardiovascular disease via its influence on health behaviours. The aim of this study was to estimate the associations between traditional and novel neighbourhood built environment metrics and clinically assessed cardio-metabolic risk factors among a sample of adults in Canada. A total of 7171 participants from Albertas Tomorrow Project living in Alberta, Canada, were included. Cardio-metabolic risk factors were clinically measured. Two composite built environment metrics of traditional walkability and space syntax walkability were calculated. Among men, space syntax walkability was negatively associated with systolic and diastolic blood pressure (b = −0.87, 95% CI -1.43, −0.31 and b = −0.45, 95% CI -0.86, −0.04, respectively). Space syntax walkability was also associated with lower odds of overweight/obese among women and men (OR = 0.93, 95% CI 0.87, 0.99 and OR = 0.88, 95% CI 0.79, 0.97, respectively). No significant associations were observed between traditional walkability and cardio-metabolic outcomes. This study showed that the novel built environment metric based on the space syntax theory was associated with some cardio-metabolic risk factors. • The built environment may be associated with the risk of CVD via health behaviours. • Space syntax walkability was associated with lower odds of overweight/obesity. • Space syntax walkability was negatively associated with blood pressure in men. [ABSTRACT FROM AUTHOR]