OBJECTIVE - Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with a substantially elevated risk of adverse health outcomes for both mothers and offspring. Physical activity may contribute to the prevention of GDM and thus is crucial for dissecting the vicious circle involving GDM, childhood obesity, and adulthood obesity, and diabetes. Therefore, we aimed to systematically review and synthesize the current evidence on the relation between physical activity and the development of GDM. RESEARCH DESIGN AND METHODS - Medline, EMBASE, and Cochrane Reviews were searched from inception to 31 March 2010. Studies assessing the relationship between physical activity and subsequent development of GDM were included. Characteristics including study design, country, GDM diagnostic criteria, ascertainment of physical activity, timing of exposure (prepregnancy or early pregnancy), adjusted relative risks, CIs, and statistical methods were extracted independently by two reviewers. RESULTS - Our search identified seven prepregnancy and five early pregnancy studies, including five prospective cohorts, two retrospective case-control studies, and two cross-sectional study designs. Prepregnancy physical activity was assessed in 34,929 total participants, which included 2,813 cases of GDM, giving a pooled odds ratio (OR) of 0.45 (95% CI 0.28-0.75) when the highest versus lowest categories were compared. Exercise in early pregnancy was assessed in 4,401 total participants, which included 361 cases of GDM, and was also significantly protective (0.76 [95% CI 0.70-0.83]). CONCLUSIONS - Higher levels of physical activity before pregnancy or in early pregnancy are associated with a significantly lower risk of developing GDM. © 2011 by the American Diabetes Association.