This international, multicenter, cross-sectional study comprising 1346 adult in- and outpatients with major depressive disorder (MDD) investigated the association between MDD as primary diagnosis and comorbid post-traumatic stress disorder (PTSD). In a cross-sectional data collection process, the presence of comorbid PTSD was determined by the Mini International Neuropsychiatric Interview (MINI) and the patients’ socio-demographic, clinical, psychopharmacological, and response information were obtained. Clinical features between MDD with and without concurrent PTSD were compared using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. 1.49% of the MDD patients suffered from comorbid PTSD. Significantly more MDD + comorbid PTSD patients exhibited atypical features, comorbid anxiety disorders (any comorbid anxiety disorder, panic disorder, agoraphobia, and social phobia), comorbid bulimia nervosa, current suicide risk, and augmentation treatment with low-dose antipsychotic drugs. In the binary logistic regression analyses, the presence of atypical features (odds ratio (OR) = 4.49, 95%CI:1.01–20.12; p≤.05), any comorbid anxiety disorder (OR = 3.89, 95%CI:1.60-9.44; p = .003), comorbid panic disorder (OR = 6.45, 95%CI:2.52–16.51; p = .001), comorbid agoraphobia (OR = 6.51, 95%CI:2.54-16.68; p≤.001), comorbid social phobia (OR = 6.16, 95%CI:1.71–22.17; p≤.001), comorbid bulimia nervosa (OR = 10.39, 95%CI:1.21–88.64; p = .03), current suicide risk (OR = 3.58, 95%CI:1.30–9.91; p = .01), and augmentation with low-potency antipsychotics (OR = 6.66, 95%CI:2.50–17.77; p<.001) were associated with concurrent PTSD in predominant MDD. Major findings of this study were (1.) the much lower prevalence rate of comorbid PTSD in predominant MDD compared to the reverse prevalence rates of concurrent MDD in primary PTSD, (2.) the high association to comorbid anxiety disorders, and (3.) the increased suicide risk due to concurrent PTSD.