Background: Cannabis use has been linked to impaired driving and fatal accidents. Prior evidence suggests the potential for population-wide effects of the annual cannabis celebration on April 20th (‘4/20’), but evidence to date is limited. Methods: We used data from the Fatal Analysis Reporting System for the years 1975-2016 to estimate the impact of ‘4/20’ on drivers involved in fatal traffic crashes occurring between 16:20 and 23:59 hours in the USA. We compared the effects of 4/20 with those for other major holidays, and evaluated whether the impact of ‘4/20’ had changed in recent years. Results: Between 1992 and 2016, ‘4/20’ was associated with an increase in the number of drivers involved in fatal crashes (IRR 1.12, 95% CI 0.97 to 1.28) relative to control days 1 week before and after, but not when compared with control days 1 and 2 weeks before and after (IRR 1.05, 95% CI 0.92 to 1.28) or all other days of the year (IRR 0.98, 95% CI 0.88 to 1.10). Across all years we found little evidence to distinguish excess drivers involved in fatal crashes on 4/20 from routine daily variations. Conclusions: There is little evidence to suggest population-wide effects of the annual cannabis holiday on the number of drivers involved in fatal traffic crashes. o̧pyright Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.