AbstractProblem statementSeeking Safety (SS) is a widely implemented cognitive‐behavioral therapy for comorbid post‐traumatic stress disorder (PTSD) and substance use disorder (SUD). It is a present‐focused coping skills model that is highly flexible, with varied methods of delivery, to maximize acceptability and client access. The purpose of this meta‐analysis is to examine the effect of SS on comorbid PTSD and SUD across randomized control trials (RCTs). In addition, ours is the first meta‐analysis to examine the dose‐response of SS by comparing delivery of all 25 SS topics versus fewer.Methods and designArticles published before January 2, 2023 (CINAHLn= 16, PsycINFOn= 31, MEDLINEn= 27, Cochranen= 38, and Scopusn= 618) were searched. Seven studies were included for meta‐analysis and dose‐response analysis.ResultsBased on effect sizes (ES), meta‐analysis revealed that SS has a medium group, time (p= .04), and time by group effect on substance use per the Addiction Severity Index at 3 months and a small effect on Clinician‐Administered PTSD Scale scores by group, a large effect by time, and a medium time by group (p= .002) effect at 6 months. Based on the pooled ES examining various measures across multiple timepoints, SS had small to medium effects on substance use by time, group, or time by group and medium to large effects on PTSD symptoms by time, group, or time by group (except for the group effect at 3‐month follow‐up). Significant effects were found for substance use by time at 3 and 6 months and for PTSD postintervention, at 6 months and 9 months by group, time, and time by group while only by time at 3 months. Meta‐regression revealed that partial dose versions of SS generally function as well as the full dose version of SS when observing long‐term effects (greater than 3 months).DiscussionFindings suggest SS has merit in treating PTSD symptoms and SUD. Based on the summarized effect sizes, SS appears more effective in reducing PTSD than substance use, which converges with the larger treatment outcome literature that consistently finds this. We explore reasons that treatment of SUD is more challenging than treating PTSD and offer suggestions for practitioners. We emphasize the need for future studies to utilize common measures and provide full details of treatment delivery for optimal comparison across studies.