INTRODUCTION Alcohol-involved motor vehicle crashes are a major cause of preventable mortality in the U.S., leading to more than 10,000 fatalities in 2013. Ignition interlocks, or alcohol-sensing devices connected to a vehicle's ignition to prevent it from starting if a driver has a predetermined blood alcohol content (BAC) level, are a promising avenue for preventing alcohol-involved driving. This study sought to assess the effects of laws requiring ignition interlocks for some or all drunk driving offenders on alcohol-involved fatal crashes. METHODS A multilevel modeling approach assessed the effects of state interlock laws on alcohol-involved fatal crashes in the U.S. from 1982 to 2013. Monthly data on alcohol-involved crashes in each of the 50 states was collected in 2014 from the National Highway Traffic Safety Administration Fatality Analysis Reporting System. Random-intercept models accounted for between-state variation in alcohol-involved fatal crash rates and autocorrelation of within-state crash rates over time. Analysis was conducted in 2015. RESULTS State laws requiring interlocks for all drunk driving offenders were associated with a 7% decrease in the rate of BAC >0.08 fatal crashes and an 8% decrease in the rate of BAC ≥0.15 fatal crashes, translating into an estimated 1,250 prevented BAC >0.08 fatal crashes. Laws requiring interlocks for segments of high-risk drunk driving offenders, such as repeat offenders, may reduce alcohol-involved fatal crashes after 2 years of implementation. CONCLUSIONS Ignition interlock laws reduce alcohol-involved fatal crashes. Increasing the spread of interlock laws that are mandatory for all offenders would have significant public health benefit.