BackgroundConcurrent use of marijuana and alcohol in drivers is of increasing concern but its role in crash causation has not been well understood.Methods Using a case–control design, we assessed the individual and joint effects of marijuana and alcohol use on fatal crash risk. Cases (n = 1944) were drivers fatally injured in motor vehicle crashes in the United States at specific times in 2006, 2007 and 2008. Controls (n = 7719) were drivers who participated in the 2007 National Roadside Survey of Alcohol and Drug Use by Drivers.ResultsOverall, cases were significantly more likely than controls to test positive for marijuana (12.2% vs. 5.9%, p < 0.0001), alcohol (57.8% vs. 7.7%, p < 0.0001) and both marijuana and alcohol (8.9% vs. 0.8%, p < 0.0001). Compared to drivers testing negative for alcohol and marijuana, the adjusted odds ratios of fatal crash involvement were 16.33 [95% confidence interval (CI): 14.23, 18.75] for those testing positive for alcohol and negative for marijuana, 1.54 (95% CI: 1.16, 2.03) for those testing positive for marijuana and negative for alcohol, and 25.09 (95% CI: 17.97, 35.03) for those testing positive for both alcohol and marijuana.ConclusionsAlcohol use and marijuana use are each associated with significantly increased risks of fatal crash involvement. When alcohol and marijuana are used together, there exists a positive synergistic effect on fatal crash risk on the additive scale.