OBJECTIVES: We estimated the injury prevention impact and cost savings associated with alcohol interlock installation in all new US vehicles. METHODS: We identified fatal and nonfatal injuries associated with drinking driver vehicle crashes from the Fatality Analysis Reporting System and National Automotive Sampling System’s General Estimates System data sets (2006-2010). We derived the estimated impact of universal interlock installation using an estimate of the proportion of alcohol-related crashes that were preventable in vehicles < 1 year-old. We repeated this analysis for each subsequent year, assuming a 15-year implementation. We applied existing crash-induced injury cost metrics to approximate economic savings, and we used a sensitivity analysis to examine results with varying device effectiveness. RESULTS: Over 15 years, 85% of crash fatalities (> 59 000) and 84% to 88% of nonfatal injuries (> 1.25 million) attributed to drinking drivers would be prevented, saving an estimated $342 billion in injury-related costs, with the greatest injury and cost benefit realized among recently legal drinking drivers. Cost savings outweighed installation costs after 3 years, with the policy remaining cost effective provided device effectiveness remained above approximately 25%. CONCLUSIONS: Alcohol interlock installation in all new vehicles is likely a cost-effective primary prevention policy that will substantially reduce alcohol-involved crash fatalities and injuries, especially among young vulnerable drivers.