Background and aim: Modafinil is best known as a sleep regulator among healthy individuals, but studies suggest that it reduces excessive daytime sleepiness in patients with brain injury. This retrospective pilot study evaluated the effectiveness of Modafinil for people with a prolonged disorder of consciousness and whether those with a traumatic brain injury did better than those with a non-traumatic brain injury.Method: Twenty four prolonged disorder of consciousness patients who were prescribed Modafinil, were assessed at least four times both before and during treatment. The Coma Recovery Scale-Revised was used to determine if patients had a disorder of consciousness and the Wessex Head Injury Matrix was used to monitor behavior during baseline and treatment periods. Patients with a traumatic brain injury (N=12) were compared with those with non-traumatic brain injury (N=12). A chi-square test with significance at 0.05 was used and when frequencies were below 5 a Fisher's Exact Test was used.Results: Cognitive improvements were noted in domains of wakefulness, awareness, concentration, tracking and following commands. Significant differences were found for the whole group between baseline and Modafinil (x(2)=9.80; p=0.002). Eleven of the 12 traumatic brain injury patients had higher Wessex Head Injury Matrix scores when on Modafinil (x(2)=8.33, p<0.004). Six non-traumatic brain injury patients had higher scores with Modafinil, two had lower scores and four showed no change. There was no significant difference in the number of patients showing an increase compared to those showing a decrease (Fisher's exact test p=0.29).Conclusion: Modafinil appears to be beneficial for enhancing cognition in prolonged disorder of consciousness patients. Traumatic brain injury patients benefited more than non-traumatic brain injury patients.