Anger and irritability are important and persistent clinical problems following traumatic brain injury (TBI). Treatment options include medications, behavioral modification, and psychotherapies, but some are impractical and none have proven efficacy with this population. We describe a randomized multi-center clinical trial testing a novel, one-on-one, 8-session psychoeducational treatment program, Anger Self-Management Training (ASMT), designed specifically for people with TBI who have significant cognitive impairment. The trial is notable for its use of a structurally equivalent comparison treatment, called Personal Readjustment and Education (PRE), which was created for the study and is intended to maximize equipoise for both participants and treaters. Fidelity assessment is conducted in real time and used in therapist supervision sessions. The primary outcome is change in self-reported anger on validated measures from pre-treatment to 1 week after the final session. Secondary outcomes include participant anger as reported by a significant other; emotional distress in domains other than anger/ irritability; behavioral functioning; and quality of life. An interim assessment after the 4th session will allow examination of the trajectory of any observed treatment effects, and a follow-up assessment 2 months after the end of intervention will allow examination of persistence of effects. A treatment enactment phase, in which participants are interviewed several months after the last therapy session, is designed to provide qualitative data on whether and to what extent the principles and techniques learned in treatment are still carried out in daily life.