OBJECTIVE: To report on the prevalence acute and chronic substance use among patients attending an emergency department (ED) in Mexico City because of a road traffic injury (RTI) and possible effect modifiers for the relationship between acute alcohol and cannabis use and RTI. MATERIALS AND METHODS: Adult RTI patients, admitted to an ED (January to April 2022). Breath Alcohol Concentration and six types of drugs were assessed using a saliva screen test. Patients also self-reported their alcohol and drug use. RESULTS: 13.9% reported an alcohol use disorder in the last 12 months. Acute alcohol use was frequent, with 18.9% being positive. We found a large association between habitual and acute substance use. In a case-crossover analysis, there was no significant effect modification. CONCLUSION: Patients positive for substance use at entry to the ED should have a comprehensive evaluation of their substance abuse habits and a referral to a mental health specialist.