Background Prolonged Exposure (PE) therapy is an efficacious treatment for PTSD; despite this, many clinicians do not utilize it due to concerns it could cause patient decompensation. Method Data were pooled from four published well‐controlled studies of female assault survivors with chronic PTSD (n = 361) who were randomly assigned to PE, waitlist (WL), or another psychotherapy, including cognitive processing therapy (CPT), Eye Movement and Desensitization Reprocessing (EMDR), or the combination of PE plus stress inoculation training (SIT) or PE plus cognitive restructuring. PTSD and depression severity scores were converted to categorical outcomes to evaluate the proportion of participants who showed reliable symptom change (both reliable worsening and reliable improvement). Results The majority of participants completing one of the active treatments showed reliable improvement on both PTSD and depression compared to WL. Among treatment participants in general, as well as those who received PE, reliable PTSD worsening was nonexistent and the rate of reliable worsening of depression was low. There were no differences on any outcome measures among treatments. By comparison, participants in WL had higher rates of reliable symptom worsening for both PTSD and depression. Potential alternative explanations were also evaluated. Conclusions PE and a number of other empirically supported therapies are efficacious and safe treatments for PTSD, reducing the frequency of which symptom worsening occurs in the absence of treatment.