Background: Trauma-focused treatments for posttraumatic stress disorder (PTSD) are commonly delivered either once or twice a week. Initial evidence suggests that session frequency affects treatment response, but very few trials have investigated the effect of session frequency. The present study’s aim is to compare treatment outcomes of twice-weekly versus once-weekly sessions of two treatments for PTSD related to childhood trauma, imagery rescripting (ImRs) and eye movement desensitization and reprocessing (EMDR). We hypothesize that both treatments will be more effective when delivered twice than once a week. How session frequency impacts treatment response, whether treatment type moderates the frequency effect, and which treatment type and frequency works best for whom will also be investigated. Methods: The IREM-Freq trial is an international multicenter randomized clinical trial conducted in mental healthcare centers across Australia, Germany, and the Netherlands. We aim to recruit 220 participants, who will be randomized to one of four conditions: (1) EMDR once a week, (2) EMDR twice a week, (3) ImRs once a week, or (4) ImRs twice a week. Treatment consists of 12 sessions. Data are collected at baseline until one-year follow-up. The primary outcome measure is clinician-rated PTSD symptom severity. Secondary outcome measures include self-reported PTSD symptom severity, complex PTSD symptoms, trauma-related cognitions and emotions, depressive symptoms, dissociation, quality of life, and functioning. Process measures include memory, learning, therapeutic alliance, motivation, reluctance, and avoidance. Additional investigations will focus on predictors of treatment outcome and PTSD severity, change mechanisms of EMDR and ImRs, the role of emotions, cognitions, and memory, the optimization of treatment selection, learned helplessness, perspectives of patients and therapists, the network structure of PTSD symptoms, and sudden treatment gains. Discussion: This study will extend our knowledge on trauma-focused treatments for PTSD related to childhood trauma and, more specifically, the importance of session frequency. More insight into the optimal session frequency could lead to improved treatment outcomes and less dropout, and in turn, to a reduction of healthcare costs. Moreover, the additional investigations will broaden our understanding of how the treatments work and variables that affect treatment outcome. Trial registration: Netherlands Trial Register NL6965, registered 25/04/2018.