As part of a preliminary investigation on the effects of methylphenidate on brain activation during a working memory (WM) task in patients with traumatic brain injury (TBI), patients with TBI received 15 mg of methylphenidate (N = 4) or placebo (N = 5) twice a day for one month in a double-blind, placebo-controlled design. Brain activation was assessed at pre-treatment and on the final treatment day using functional magnetic resonance imaging (fMRI) with an N-back task using faces as stimuli. In a whole brain voxel-wise analysis, methylphenidate, compared to placebo, produced a decrease in brain activation for the 2-load minus 0-load contrast in the anterior cingulate, thalamus, cuneus and cerebellum, regions associated with WM performance. Further, an a priori region of interest analysis with small volume correction found reduced activation in the anterior cingulate. Although based on a small sample size, these preliminary findings suggest methylphenidate may increase processing efficiency associated with cognitive control during WM tasks in patients with TBI.