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Background: Lifestyle genomics (LGx) is a science that explores interactions between genetic variation, lifestyle components such as physical activity (PA), and subsequent health- and performance-related outcomes. The objective of this study was to determine whether an LGx intervention could motivate enhanced engagement in PA to a greater extent than a population-based intervention. Methods: In this pragmatic randomized controlled trial, participants received either the standard, population-based Group Lifestyle BalanceTM (GLB) program intervention or the GLB program in addition to the provision of LGx information and advice (GLB + LGx). Participants (n = 140) completed a 7-day PA recall at baseline, 3, 6, and 12 months. Data from the PA recalls were used to calculate metabolic equivalents (METs), a measure of energy expenditure. Statistical analyses included split plot analyses of covariance and binary logistic regression (generalized linear models). Differences in leisure time PA weekly METs, weekly minutes of moderate + high-intensity PA, and adherence to PA guidelines were compared between groups (GLB and GLB + LGx) across the 4 time points. Results: Weekly METs were significantly higher in the GLB + LGx group (1,114.7 ± 141.9; 95% CI 831.5-1,397.8) compared to the standard GLB group (621.6 ± 141.9 MET/week; 95% CI 338.4-904.8) at the 6-month follow-up (p = 0.01). All other results were non-significant. Conclusions: The provision of an LGx intervention resulted in a greater weekly leisure time PA energy expenditure after the 6-month follow-up. Future research should determine how this could be sustained over the long-term. Clinical Trial Registration: NCT03015012.