BACKGROUND: Decision makers at multiple levels need information about which clinical preventive services matter the most so that they can prioritize their actions. This study was designed to produce comparable estimates of relative health impact and cost effectiveness for services considered effective by the U.S. Preventive Services Task Force and Advisory Committee on Immunization Practices. METHODS: The National Commission on Prevention Priorities (NCPP) guided this update to a 2001 ranking of clinical preventive services. The NCPP used new preventive service recommendations up to December 2004, improved methods, and more complete and recent data and evidence. Each service received 1 to 5 points on each of two measures--clinically preventable burden and cost effectiveness--for a total score ranging from 2 to 10. Priorities for improving delivery rates were established by comparing the ranking with what is known of current delivery rates nationally. RESULTS: The three highest-ranking services each with a total score of 10 are discussing aspirin use with high-risk adults, immunizing children, and tobacco-use screening and brief intervention. High-ranking services (scores of 6 and above) with data indicating low current utilization rates (around 50% or lower) include: tobacco-use screening and brief intervention, screening adults aged 50 and older for colorectal cancer, immunizing adults aged 65 and older against pneumococcal disease, and screening young women for Chlamydia. CONCLUSION: This study identifies the most valuable clinical preventive services that can be offered in medical practice and should help decision-makers select which services to emphasize.