Objective: Adults 65 years of age and older comprise the fastest growing demographic in the United States. As substance use is projected to increase in this population, there is concern that more seniors will drive under the influence of impairing drugs. The purpose of this analysis was to characterize the drug and alcohol usage among senior drivers fatally injured (FI) in traffic collisions. Methods: Data from the Fatality Analysis Reporting System were analyzed from 2008 to 2012. Commonly used classes and specific drugs were explored. Rates of drug use, multiple drugs, concomitant drug and alcohol use, and alcohol use alone were generated using Poisson regression with robust error variance estimation. Rates were compared to a reference population of FI middle-aged drivers (30 to 50 years old) using rate ratios. Results: Drug use among FI senior drivers occurred in 20.0% of those tested. Among drug-positive FI senior drivers, narcotics and depressants were frequent. The prevalence of testing positive for any drug, multiple drugs, combined drug and alcohol, and alcohol use alone among FI seniors were 47% less (relative risk [RR] = 0.53, 95% confidence interval [CI], 0.47, 0.62), 59% less (RR = 0.41, 95% CI, 0.34, 0.51), 87% less (RR = 0.13, 95% CI, 0.09, 0.19), and 77% less (RR = 0.23, 95% CI, 0.19, 0.28), respectively, compared to FI middle-aged drivers. Conclusions: Though overall drug use is less common among FI senior drivers relative to FI middle-aged drivers, driving under the influence of drugs may be a relevant traffic safety concern in a portion of this population.