© 2019 American Journal of Preventive Medicine Context: Anxiety symptoms and disorders are highly prevalent and costly. Prospective studies suggest that physical activity may prevent anxiety development; however, this body of literature has not been reviewed comprehensively. Evidence acquisition: Studies measuring physical activity at baseline and anxiety at a designated follow-up at least 1 year later were located using MEDLINE, PsycINFO, and CINAHL Complete through June 2018. Evidence synthesis: Data were analyzed July¿December 2018. Study quality was assessed using Q-Coh. Among studies of adults, a random-effects meta-analysis was conducted for crude and the most fully adjusted models for three outcomes: self-reported anxiety symptoms, a diagnosis of any anxiety disorder, and a diagnosis of generalized anxiety disorder. As there were few studies with diverse samples and outcome measures, findings were elaborated with a critical narrative review of all studies. Twenty-four studies (median follow-up, 4.75 years) of >80,000 unique individuals were included in the systematic review; thirteen were included in the meta-analyses. Six studies were assessed as low quality, nine as acceptable, and nine as good. From adjusted models, odds of elevated anxiety symptoms (OR=0.8742, 95% CI=0.7731, 0.9886, n=9), any anxiety disorder (OR=0.6626, 95% CI=0.5337, 0.8227, n=3), and generalized anxiety disorder specifically (OR=0.5438, 95% CI=0.3231, 0.9153, n=3) were significantly lower after physical activity exposure. Conclusions: Available evidence suggests that engaging in physical activity protects against anxiety symptoms and disorders. However, notable challenges in the current evidence base include issues regarding exposure and outcome measures, consistent adjustment for putative confounders, representativeness of samples, and attrition bias, which warrant further research.