Summary: Post-traumatic stress disorder (PTSD) is a common and debilitating condition that is estimated to affect over 7% of British military veterans and 17% of those who have deployed in a combat role, compared to 4.4% of the civilian population. Unfortunately, many veterans with PTSD remain symptomatic despite having received evidence-based interventions and there is an urgent need to develop more effective treatments. Modular motion-assisted memory desensitisation and reconsolidation (3MDR) is a new treatment for PTSD based on virtual reality exposure therapy and eye movement desensitization and reprocessing (EMDR), embedded in a novel context in which the patient walks on a treadmill whilst interacting with a series of self-selected images that are displayed on a large screen. Preliminary results from research conducted by the originators of 3MDR in the Netherlands were promising. We, therefore, decided to explore the potential efficacy of 3MDR further by conducting a randomised controlled trial with nested process evaluation to assess fidelity, adherence and factors that influence outcome. Forty-two military veterans living in South Wales who continued to experience service-related PTSD following treatment with trauma-focused psychological therapy took part in the study. Participants completed a baseline assessment and were then randomised to receive 3MDR immediately or after a delay of 14 weeks, with follow-up assessments occurring at 12 and 26 weeks post randomisation. Retention rates were very high; 83% (35 participants) at 12 weeks and 86% (36 participants) at 26 weeks. Eleven of the participating veterans and all six of the 3MDR therapists participated in a single qualitative interview, designed to provide greater understanding about 3MDR, the experience of receiving it and of delivering 3MDR, and of being involved in the research trial. Participating veterans were purposively selected to learn from as wide a range of individuals as possible, with different characteristics and experiences. PTSD symptom severity was statistically and clinically significantly better for the immediate treatment group (37% average reduction of PTSD symptoms after receipt of 3MDR) than the delayed treatment group (14% average reduction in PTSD symptoms whilst waiting for 3MDR) at the 12-week follow-up point, which shows a 19% greater reduction in PTSD symptoms for the immediate treatment group over the delayed treatment group at that point. The delayed treatment group experienced an average 28% further PTSD symptom reductions following 3MDR and the immediate treatment group maintained their improvement at 26-week follow-up. It is important to note, however, that not all participants improved following 3MDR and some reported increased symptoms. The likely effect size of 3MDR was found to be 0.65, representing a moderate treatment effect despite it being tested in veterans with treatment-resistant PTSD. 3MDR was found to be acceptable to most, but not all, participants and to all the therapists delivering the intervention, albeit with recommendations on what could be done to enhance its effect and acceptability. Key findings in this regard included the appropriate assessment and selection of potential candidates for 3MDR, enhanced preparation in advance of 3MDR, the number of treatment sessions available, support between sessions and greater flexibility with respect to content of later 3MDR sessions. This study has shown emerging evidence of 3MDR being effective for treatment resistant PTSD and further research through a pragmatic effectiveness randomised controlled trial is now required to determine its true effectiveness and optimal delivery.