Concurrent posttraumatic stress disorder and substance use disorder (PTSD/SUD) in US military veterans represents an urgent public health issue associated with significant clinical challenges. Although previous research has shown that veterans with PTSD/SUD endorse more psychosocial risk factors and fewer protective factors than veterans with neither or only one of these disorders, no study has applied a comprehensive framework to characterize the vocational, financial, and social well-being of veterans with PTSD/SUD. Furthermore, it is not fully known how well-being among veterans with PTSD/SUD compares to that of veterans with posttraumatic stress disorder (PTSD) only, substance use disorder (SUD) only, or neither disorder. This cross-sectional observational study analyzed data from the National Post-Deployment Adjustment Survey, which recruited a random national sample of US veterans who served on/after September 11, 2001. Participants (weighted N= 1,102) self-reported sociodemographic, clinical, and military background information in addition to aspects of their vocational, financial, and social well-being. Veterans with PTSD/SUD were particularly likely to report lifetime experiences of homelessness, violent behavior, suicidal ideation, and suicide attempts. Veterans with PTSD/SUD reported worse social well-being than the PTSD-only, SUD-only, and neither-disorder groups. They also reported worse vocational and financial well-being than veterans with SUD only or with neither disorder but did not significantly differ from the PTSD-only group on vocational or financial well-being. The findings underscore the importance of assessing multiple aspects of well-being in veterans with PTSD and/or SUD. The findings also point to promising treatment targets to improve psychosocial functioning and overall quality of life among veterans with PTSD and/or SUD.(PsycInfo Database Record (c) 2022 APA, all rights reserved)