The collaborative, anonymous, case-control study was intended to determine the prevalence of opiates, cocaine metabolites, cannabinoids and amphetamines in the urine of drivers injured in road accidents and to compare these values with those of non-accident subjects ("patients") in France. Recruitment was performed nationwide in the emergency departments of five hospitals and comprised 296 "drivers" aged 18 to 35 and 278 non-traumatic "patients" in the same age range. Females represented 28.4% of "drivers" and 44.2% of "patients." Screening for drugs in urine was performed by fluorescence polarization immunoassays in each center. Each positive result was verified using gas chromatography-mass spectrometry (GC-MS), in a single laboratory. Statistical analysis comprised single-step logistic regression and simultaneously took account of confounding factors and the final differences in prevalence values between the two populations or different subgroups. Cannabinoids were found in 13.9% of drivers (16.0% of males and 8.3% of females, p < 0.05) and 7.5% of patients (12.3% of males, 1.6% of females, p < 0.0001); only in females was this prevalence higher in injured drivers than in patients (p < 0.05). Opiates were present in 10.5% of drivers' and 10.4% of patients' urine samples (NS), and were more frequent in urine samples positive for cannabinoids, in drivers (p < 0.01) as well as in patients (p < 0.001). The prevalence of cocaine metabolites in drivers and patients was 1.0 and 1.1% and that of amphetamines 1.4 and 2.5%, respectively. No causal relationship between drugs and accidents should be inferred from this retrospective study. Nevertheless, the high prevalence of cannabis and opiate (licit or illicit) use in young people, whether injured drivers or patients, has potential implications for road traffic safety in France. Cocaine and amphetamines did not appear to be a major problem, unlike the experience in other countries.