The neuropsychological performance of 119 patients with severe closed traumatic brain injury (TBI) who had received toxicology screens at the time of trauma centre admission was examined. Three groups were created: normal screen, positive alcohol screen, or positive abused drugs screen (with or without the presence of alcohol). The admitting Glasgow Coma Scale (GCS) score was significantly lower in the positive alcohol screen group than the normal screen group, while the three groups did not differ in length of post-traumatic amnesia (PTA) or years of education. Neuropsychological assessment was conducted during inpatient rehabilitation, following resolution of PTA. Normal screen patients obtained significantly better scores than the abused-drugs patients on the Full Scale IQ (FIQ) and Verbal IQ (VIQ) indices of the Wechsler Adult Intelligence Scale-Revised and the Verbal Memory, General Memory, Attention-Concentration, and Delayed Recall indices of the Wechsler Memory Scale-Revised. Normal screen patients also scored significantly higher than positive alcohol screen patients on FIQ and VIQ indices and all five indices from the Wechsler Memory Scale-Revised. These data suggest the existence of an additive effect of substance abuse on neuropsychological outcome in TBI. Findings have potential implications for both acute management and rehabilitation of TBI.