Aims: To clarify alcohol and illicit drug use within the emergency room population in three different regions in The Netherlands, focusing on whether interventions for these substances should be region specific. Methods: Alcohol and illicit drug use were assessed using a self-report questionnaire filled in by the patients, and by combining self-report with staff judgement on alcohol and illicit drug use. Results: Data on alcohol use (self-reported and staff judgement combined) resulted in prevalence rates of 4.9–18.2%. Patients positive for alcohol are more likely to be male, aged 48–58 years, more likely to be a frequent excessive drinker, and to have injuries as a result of violence. Patients positive for illicit drugs are more likely to be male, aged 28–38 years, unemployed, and frequent excessive drinkers. Among men aged 18–35 years with a Dutch cultural background, some differences emerge regarding alcohol consumption between the various hospitals, but most variation exists in the case of illicit drug use. Conclusions: This paper confirms that the emergency room seems to provide an opportunity to initiate interventions regarding alcohol use and seems to suggest that this is independent of the region concerned. However, in the case of illicit drug use interventions seem to be more region specific.