Importance Diabetic macular edema (DME) is a leading cause of vision loss in persons with diabetes mellitus. Although there are national estimates for the prevalence of diabetic retinopathy and its risk factors among persons with diabetes, to our knowledge, no comparable estimates are available for DME specifically. Objectives To estimate the prevalence of DME in the US population and to identify associated risk factors. Design, Setting, and Participants A cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and valid fundus photographs in the 2005 to 2008 National Health and Nutrition Examination Survey. Main Outcomes and Measures The overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex. Results Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746 000 persons in the US 2010 population aged 40 years or older. We identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis showed that the odds of having DME were higher for non-Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19-5.84; P = .02). Elevated levels of glycosylated hemoglobin A 1c (OR, 1.47; 95% CI, 1.26-1.71 for each 1%; P P Conclusions and Relevance These results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A 1c , and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation is even more important for those at higher risk for DME.