Background and Significance: Posttraumatic stress disorder (PTSD) impacts both individual and relationship functioning. In romantic relationships, PTSD can impact both partners, causing disruption within the relationship that can in turn worsen PTSD symptomology. Poor relationship functioning places Veterans at greater risk for other negative outcomes such as suicide, homelessness and substance use disorders. Veterans seeking treatment for PTSD often want to improve their intimate relationships and express the desire to involve close others in treatment. Treatment outcomes are in fact enhanced when both partners engage in treatment together. One treatment option for Veterans and their partners is brief Cognitive-Behavioral Conjoint Therapy (bCBCT), a trauma focused 8-session psychotherapy for PTSD that is delivered in a dyadic format to an individual with PTSD and a loved one—typically an intimate partner. This intervention has been rolled out in the VA and is consistently efficacious in improving PTSD, however the effects of bCBCT on relationship functioning are less robust with small effect sizes, especially among Veterans. Novel pharmacological augmentation strategies that simultaneously target mechanisms of PTSD and relationship functioning may increase the potency and impact of bCBCT. Intranasal oxytocin is one such novel agent, as it influences multiple processes relevant to PTSD recovery, such as fear extinction, and relationship functioning, including but not limited to trust, empathy, and positive communication. Intranasal oxytocin is therefore ideally suited to enhance the effects of bCBCT. The goal of this proposal is to examine the efficacy of bCBCT augmented with intranasal oxytocin for improving Veterans' PTSD symptoms and relationship satisfaction among both Veterans and their intimate partners. It is hypothesized that the bCBCT + oxytocin condition will outperform bCBCT + placebo with respect to Veterans' PTSD symptoms and both Veterans' and partners' relationship satisfaction. Additionally, this study will explore the impact of intranasal oxytocin on Veterans' psychosocial functioning and potential mechanisms of action (i.e., communication skills, empathy, and trust). Methods: This study will recruit 120 couples from the VA San Diego Healthcare System for a placebo-controlled four-year randomized clinical trial. Eligible couples will consist of a Veteran with PTSD and the Veteran's intimate partner. Veterans will self-administer 40 international units of intranasal oxytocin (n = 60 dyads) or placebo (n = 60 dyads) 30 minutes before each of the 8 bCBCT sessions. PTSD, relationship satisfaction, psychosocial functioning, and potential mechanisms of action (communication skills, empathy, and trust) will be assessed at baseline, mid-treatment, post-treatment, 3-month, and 6-month follow-up. Impacts on Veteran Health Care: This proposal directly addresses the VA priority of advancing innovations in VHA health care, as well as the need...