Objective: To explore whether psychosocial challenges impact effects of vocational rehabilitation in Veterans with Posttraumatic Stress Disorder (PTSD). Methods: A post hoc exploratory analysis of possible moderators of treatment was conducted on outcomes from a randomized, controlled trial of Individual Placement and Support in Veterans with PTSD. Results: When examining groups within each moderator, there was a greater IPS supportive employment benefit in gaining competitive employment for those with inadequate transportation (number needed to treat [NNT] = 1.5) and inadequate housing (NNT = 1.5) compared with the main finding of the pilot study (NNT = 2.07). Compared with the main finding of the pilot study, there was no greater advantage of IPS for those with adequate transportation (NNT = 2.4) or adequate housing (NNT = 2.4). Compared with the main finding in the pilot study, those without a family care burden had a greater benefit from IPS (NNT = 1.4) and those with family care burden had a reduced treatment effect (NNT = 3.3). Conclusions and Implications for Practice: These results are exploratory and are not intended to guide clinical decision-making, but rather offer a potentially useful strategy in the design of larger trials of IPS. © 2014 American Psychological Association.