BACKGROUND AND METHODS: Although Resick et al. [Resick, P.A., Nishith, P., Weaver, T.L., Astin, M.C., Feuer, C.A., 2002. A comparison of cognitive-processing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims. J. Consult. Clin. Psychol. 70, 867-879.] reported comparable results for treating rape-related posttraumatic stress disorder (PTSD) using either cognitive-processing therapy (CPT) or prolonged exposure (PE), there was some suggestion that CPT resulted in better outcomes than PE for certain aspects of trauma-related guilt. The present study revisited these findings to examine whether this effect was a function of improvement in a subset of participants with both PTSD and major depressive disorder (MDD). RESULTS: Results indicated that CPT was just as effective in treating "pure" PTSD and PTSD with comorbid MDD in terms of guilt. Clinical significance testing underscored that CPT was more effective in reducing certain trauma-related guilt cognitions than PE. LIMITATIONS: Findings cannot be generalized to men, and only one measure of guilt was used. CONCLUSIONS: The observed superiority of CPT over PE for treating certain guilt cognitions was not due to participant comorbidity. Further research is recommended to untangle the relationship between guilt, depression and differential response to treatment in PTSD following sexual assault trauma.