Objectives: We sought to examine the gender differences between C - reactive protein (CRP) and muscle strengthening activity (MSA) in U.S. adults (≥20 years of age) Background: Elevated levels of CRP have been shown to be associated with an increase in risk of cardiovascular disease (CVD). Studies analyzing the relationship between physical activity (PA) and CRP by gender have produced mixed results. Methods: The sample (n=9,135) included participants in the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Three categories of reported MSA participation were created: no MSA (referent group), some MSA (≥1 to/wk), and meeting the 2008 Department of Health and Human Services (DHHS) recommendation (>2 d/wk). The dependent variable was elevated CRP (>3 to 10 mg/L). Results: Gender stratified analysis revealed significantly lower odds of having elevated CRP for women reporting some MSA (OR 0.61; 95% CI 0.45-0.83, P=0.0023), or volumes of MSA meeting the DHHS recommendation (OR 0.66; 95% CI 0.54-0.82, P=0.0004). Significantly lower odds of men having elevated CRP was observed in those reporting MSA volumes meeting the recommendation (OR 0.73; 95% CI 0.61-0.88, P=0.0011). Following adjustment for waist circumference (WC) these odds remained significant in men but not women. Conclusions: Women reporting any MSA were found to have lower odds of having elevated CRP when compared to those reporting no MSA prior to adjustment for WC. Significantly lower odds in men were only observed in those meeting the recommendation. These results suggest that WC may mediate the associations between MSA and CRP and this relationship may be stronger in women.