Study Objectives: Obstructive sleep apnea (OSA) is a common condition with significant symptoms and long-term adverse cognitive, mental health, vascular, and respiratory sequelae. Physical activity has been recognized as a key determinant for good health and has been associated with lower risk of these sequelae. We hypothesized that increased physical activity may be associated with a decreased prevalence of OSA. Methods: This cross-sectional study used baseline questionnaire data fromthe OntarioHealth Study, a population-based cohort of residents ofOntario,Canada. Participants were adults who provided lifestyle, medical, socio-demographic, and sleep health information. The study sample consisted of 155,448 men (39.8%) and women (60.2%). The prevalence of physician-diagnosed OSA in this cohort was 6.9%. Logistic regression models were used to investigate the association of OSA with physical activity. Missing data were imputed using a multiple imputation by chained equation approach. Results: Inmultivariable analyses adjusted for potential confounding factors, increased total physical activity (metabolic equivalent [h/wk]) (odds ratio [OR] = .98, 95% confidence interval [CI] = .96 to 1.00), vigorous-intensity activity (OR = .98, 95% CI = .97 to 1.00), and walking (OR = .98, 95% CI = .96 to 1.00) were all associated (all P ≤ .045) with decreased prevalence of OSA. Moderate-intensity activity was not associated with risk of OSA (P = .826). Conclusions: Independent of known risk factors for OSA, including body mass index, increased levels of physical activity, including walking, were associated with a prevalence of OSA. Our results highlight the importance of physical activity as a preventive measure for sleep apnea.