OBJECTIVE Alcohol-impaired driving results in thousands of deaths annually. Alcohol ignition interlocks require a negative breath test to start a vehicle's engine, and 44 states have mandated some form of interlock law for drivers convicted of driving while intoxicated (DWI). The objective of this study was to estimate the association between interlock laws and fatal impaired-driving crashes. METHODS Differences in three interlock laws were evaluated by comparing alcohol-impaired passenger vehicle drivers involved in fatal crashes between 2001 and 2019 in the United States across state and time. State/time differences unrelated to interlock laws were controlled for by fitting a Poisson model. The exposure measure was the number of passenger vehicle drivers in fatal crashes that did not involve impaired drivers. Laws requiring interlocks for drivers convicted of DWI covered: repeat offenders, repeat offenders and high-BAC offenders, all offenders, or none. RESULTS The number of states with all-offender interlock laws during the study period went from three in 2001 to 29 in 2019, and the number of states with any of the three laws increased from 16 to 44. All-offender laws were associated with 26% fewer drivers with 0.08+ BAC involved in fatal crashes, compared with no law. Repeat-offender laws were associated with a 9% reduction in impaired drivers, compared with no law. Repeat and high-BAC laws were associated with a 20% reduction in impaired drivers in fatal crashes, compared with no law. CONCLUSION Laws mandating alcohol ignition interlocks, especially those covering all offenders, are an effective impaired-driving countermeasure that reduces the number of impaired drivers in fatal crashes.