In contrast to concerns that cognitive limitations and neurobehavioral symptoms (NBS) associated with traumatic brain injury (TBI) may inhibit treatment effectiveness, a recent study found prolonged exposure (PE) led to large reductions in posttraumatic stress disorder (PTSD) symptoms among Iraq-Afghanistan veterans with a range of TBI severity (article by Wolf, Kretzmer, Crawford, Thors, Wagner, Strom, Eftekhari, Klenk, Hayward, and Vanderploeg [J Trauma Stress 28:339–347, 2015]). We further examined this sample of 69 veterans to determine whether system, veteran, and therapist factors predicted clinically significant responses. Results of hierarchical, logistic regressions revealed that therapist training in PE and lower service connection were associated with increased odds of large decreases in PTSD symptoms after adjusting for the robust effect of PE sessions completed. Other patient-level factors including age, time since injury, and baseline NBS were unrelated to significant improvements. Findings emphasized the impact of PE dosage, indicated greater mastery of the protocol was beneficial, and showed that service connection could impede self-reported, clinically significant change during PE in this important cohort.