Magnetic resonance (MR) quantitative neuroimaging analysis was undertaken with a large group of normal (n = 197) and traumatically brain injured (TBI, n = 99) adults. Of the TBI subjects 18 patients were identified with a history of substance-related abuse (TBI/Abuse group). Both the TBI/ Abuse group and the remaining sample of TBI patients (n = 81, TBI/Non-abuse group) without a history of substance-related abuse differed significantly from the control group on most quantitative MR imaging analyses. The TBI/Abuse group displayed the greatest degree of atrophic change. However, the TBI/Abuse group had a significantly lower Glasgow Coma Scale (GCS) score, ostensibly suggesting that those with substance-related abuse suffered more severe brain injury than non-abuse TBI patients. When a subset (n = 18) of the TBI/Non-abuse group was matched by GCS, gender and age to the TBI/Abuse group, both groups differed significantly from the control group on most morphometric measures, but did not differ from one another. Results are discussed in terms of the potential adverse role that substance-related abuse, particularly alcohol, plays in the individual who sustains traumatic injury to the brain.