Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic features frequently fail to respond to antidepressants. Previous research has shown that these patients improve significantly after monotherapy with two atypical antipsychotics, olanzapine and risperidone. This study investigated the clinical outcome of another atypical antipsychotic, quetiapine, in war veterans with combat-related PTSD with psychotic features. Male war veterans (n=53) with DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was used to assess the global clinical improvement. Drug-Induced Extrapyramidal Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with quetiapine significantly reduced total and the subscales scores on the CAPS, PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic and PTSD symptoms in the patients. Our present and previous data suggest that treatment-resistant psychotic PTSD patients may improve after taking atypical antipsychotics.