Background: Opioids have been shown to impair psychomotor and cognitive functioning in healthy volunteers with no history of opioid abuse. Few or no significant effects have been found in opioid-dependant patients in experimental or driving simulation studies. The risk of road traffic crash among patients under buprenorphine or methadone has not been subject to epidemiological investigation so far. The objective was to investigate the association between the risk of being responsible for a road traffic crash and the use of buprenorphine and methadone. Methods: Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Case-control analysis comparing responsible versus non responsible drivers was conducted. Results: 72,685 drivers identified by their national health care number, involved in an injurious crash in France over the July 2005 to May 2008 period. The 196 drivers exposed to buprenorphine or methadone on the day of crash were young, essentially males, with an important co-consumption of other substances (alcohol and benzodiazepines). Injured drivers exposed to buprenorphine or methadone on the day of crash, had an increased risk of being responsible for the crash (odds ratio (OR)=2.02, 95% confidence interval (CI): 1.40, 2.91). Conclusions: Users of methadone and buprenorphine were at increased risk of being responsible for injurious road traffic crashes. This risk is probably the combined result of risky behaviors and treatments.