BACKGROUND: The Reynolds Risk Score (RRS) is one alternative to the Framingham Risk Score (FRS) for cardiovascular risk assessment. The Adult Treatment Panel III (ATP III) integrated the FRS a decade ago, but with the anticipated release of ATP IV, it remains uncertain how and which risk models will be integrated into the recommendations. We sought to define the effects in the United States population of a transition from the FRS to the RRS for cardiovascular risk assessment. METHODS: Using the National Health and Nutrition Examination Surveys, we assessed FRS and RRS in 2,502 subjects representing approximately 53.6 Million (M) men (ages 50-79) and women (ages 45-79), without cardiovascular disease or diabetes. We calculated the proportion reclassified by RRS and the subset whose LDL-C goal achievement changed. RESULTS: Compared to FRS, the RRS assigns a higher risk category to 13.9% of women and 9.1% of men while assigning a lower risk to 35.7% of men and 2% of women. Overall, 4.7% of women and 1.1% of men fail to meet newly intensified LDL-C goals using the RRS. Conversely, 10.5% of men and 0.6% of women now meet LDL-C goal using RRS when they had not by FRS. CONCLUSION: In the U.S. population the RRS assigns a new risk category for one in six women and four of nine men. In general, women increase while men decrease risk. In conclusion, adopting the RRS for the 53.6 million eligible U.S. adults would result in intensification of clinical management in 1.6 M additional women and 2.10 M fewer men.