Objectives. Identify and abstract data from randomized controlled trials (RCTs) examining treatment for posttraumatic stress disorder (PTSD) and comorbid PTSD/substance use disorder to update the previous Agency for Healthcare Research and Quality (AHRQ) report and National Center for PTSD (NCPTSD) PTSD Trials Standardized Data Repository (PTSD-Repository). Data sources. We searched PTSDpubs, Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs published from June 1, 2018, to January 26, 2022. Review methods. In consultation with AHRQ and NCPTSD, we updated the evidence tables for the PTSD-Repository by including evidence published after publication of the last update and expanding abstraction of results to include calculated standardized effect sizes. The primary publication for each RCT was abstracted; data and citations from secondary publications (i.e., companion papers) appear in the same record. We assessed risk of bias (RoB) for all newly included studies using the Revised Cochrane Risk of Bias 2 (RoB 2) tool for randomized trials. For studies already in the PTSD-Repository, we will add calculated standardized effect sizes and update RoB using the new RoB 2 tool over the next several annual updates. Results. We added 48 new RCTs examining treatments for PTSD, for a total of 437 included studies published from 1988 to July 30, 2021. Among the 48 newly added RCTs, psychotherapy interventions were the most commonly employed (50%), followed by complementary and integrative health (17%). Approximately half of studies were conducted in the United States (46%), and enrolled community participants (52%) and participants with a mix of trauma types (48%). Studies typically had sample sizes ranging from 25 to 99 participants (69%). RoB was rated as high for 52 percent of studies, 31 percent were rated as low RoB, and the remaining studies were rated as having some concerns (15%). Conclusions. This report updates the previous AHRQ report to include 48 recently published RCTs, for a total of 437 studies. This update adds comprehensive data, standardized effect sizes for PTSD outcomes, and RoB assessment for the newly included RCTs. As with the previous AHRQ update, this report will inform updates to the PTSD-Repository, a comprehensive database of PTSD trials.