Presently, 15 US states require that passenger vehicles undergo periodic safety inspections. Past studies estimating the effectiveness of these safety inspection and maintenance programs (I/M programs) in their stated aim of mitigating road accidents and fatalities have tended to rely on outdated data sets or to focus on specific geographic regions. Since inspection program effectiveness continues to be deliberated in legislative bodies across the country, this paper aims to present a replicable and data-driven quantification of the effects of I/M programs on road fatalities, applying the largest available data set, covering all 50 US states over a 44-year period. Numerous panel data regressions showed a negative correlation between the presence of state I/M programs and the fleet size–adjusted roadway fatality rate. Fixed-effects (FE) estimates suggest that states with I/M programs had 5.5% fewer roadway fatalities per 100,000 registered passenger vehicles—95% confidence interval (CI): 0.4% to 10.6%—nationwide based on nearly exhaustive data for fatal passenger vehicle accidents from 1980 to 2015. These results are complemented by an additional FE specification with fewer variables, but over a longer period. A two-stage least-squares specification is also presented that not only supports this finding but also implies a causal relationship between the presence of I/M programs and lower road fatality rates. The convergent results of the regressions presented in this paper provide compelling evidence that jurisdictions experience lower roadway fatality rates due to the presence of an active safety I/M program for passenger vehicles.