BACKGROUND Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are commonly comorbid conditions that result in greater severity, chronicity, and impairment compared with either disorder alone. However, previous research has not systematically explored the potential effects of the psychotic subtyping of MDD and comorbid PTSD. METHODS The sample in this retrospective case-control study conducted from December 1995 to August 2006 consisted of psychiatric outpatients with DSM-IV-diagnosed psychotic MDD with PTSD, psychotic MDD without PTSD, or nonpsychotic MDD with PTSD presenting for clinic intake. Clinical indices of severity, impairment, and history of illness were assessed by trained diagnosticians using the Structured Clinical Interview for DSM-IV Axis I Disorders supplemented by items from the Schedule for Affective Disorders and Schizophrenia. RESULTS In terms of current severity and impairment, the psychotic MDD with PTSD (n = 34) and psychotic MDD only (n = 26) groups were similar to each other, and both tended to be more severe than the nonpsychotic MDD with PTSD group (n = 263). In terms of history of illness, the psychotic MDD with PTSD group tended to show greater severity and impairment relative to either the psychotic MDD only or nonpsychotic MDD with PTSD groups. Furthermore, the psychotic MDD with PTSD patients had an earlier time to depression onset than patients with either psychotic MDD alone or nonpsychotic MDD with PTSD, which appeared to contribute to the poorer history of illness demonstrated in the former group. CONCLUSIONS Future research should explore the possibility of a subtype of psychotic depression that is associated with PTSD, resulting in a poorer course of illness. The current findings highlight the need for pharmacologic and psychotherapeutic approaches that can be better tailored to psychotic MDD patients with PTSD comorbidity.