Since many patients with major depressive disorder (MDD) do not satisfactorily respond to initial antidepressant monotherapy, add-on treatment strategies with other psychiatric compounds are often established. The present European multicenter cross-sectional study comprising 1410 MDD in- and outpatients investigated the prescription pattern of benzodiazepines as add-on treatment in the psychopharmacotherapy of MDD. Analyses of variance, chi-squared tests, and logistic regression analyses were conducted to examine differences in socio-demographic, clinical, and treatment characteristics between benzodiazepine users and non-users. The prescription rate for adjunctive benzodiazepine treatment amounted to 31.35%. The most often administered benzodiazepines were lorazepam (11.13%), clonazepam (6.74%), and alprazolam (6.60%). Benzodiazepine users exhibited more severe depressive symptoms expressed by a higher mean Montgomery and Åsberg Depression Rating Scale total score at study entry (26.92 ± 11.07 vs 23.55 ± 11.23, p<.0001) and at the beginning of the current major depressive episode (35.74 ± 8.08 vs 33.31 ± 7.40, p<.0001). Furthermore, they were characterized by a higher proportion of patients receiving additional augmentation/combination medications with antidepressants (40.95% vs 24.28%, p<.0001), antipsychotics (41.63% vs 18.39%, p<.0001), and low-potency antipsychotics (10.18% vs 4.75%, p<.0001). Moreover, benzodiazepine prescription was associated with older age, unemployment, inpatient treatment, suicide risk, psychotic and melancholic features, comorbid panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Taken together, our findings indicate that benzodiazepine augmentation in MDD is first of all established in severe/difficult-to-treat conditions and serves as predictor for the use of additional augmentation/combination treatment strategies.