Self-report questionnaires are economical instruments for routine outcome assessment. In this study, the performance of the German version of the Outcome Questionnaire-45 (OQ-45) and the Brief Symptom Inventory (BSI) was evaluated when applied in analysis of the outcome quality of psychiatric and psychotherapeutic interventions. Pre-post data from two inpatient samples (N = 5711) and one outpatient sample (N = 239) were analyzed. Critical differences (reliable change index) and cut-off points between functional and dysfunctional populations were calculated using the Jacobson and Truax method of calculating clinical significance. Overall, the results indicated that the BSI was more accurate than the OQ-45 in correctly classifying patients as clinical subjects. Nonetheless, even with the BSI, about 25% of inpatients with schizophrenia attained a score at admission below the clinical cut-off. Both questionnaires exhibited the highest sensitivity to psychopathology with patients with personality disorders. When considering the differences in the prescores, both questionnaires showed the same sensitivity to change. The advantage of using these self-report measures is observed primarily in assessing outpatient psychotherapy outcome. In an inpatient setting two main problems-namely, the low response rate and the scarce sensitivity to psychopathology with severely ill patients-limit the usability of self-report questionnaires.