There is a disagreement about the impact of personality disorder (PD) on treatment outcome for patients with major depressive disorder (MDD). 100 out-patients with MDD were randomized to 16 sessions of behavioural activation (BA) (n = 50) or antidepressant medication (ADM) (n = 50) in Iran. Main outcome was depression severity, measured with the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HRSD), and assessed at 0, 4, 13 and 49 weeks. Participants with comorbid PDs had higher scores on BDI and HRSD at baseline and throughout the study than participants without comorbid PD. Patients with and without comorbid personality pathology responded equally to treatment on the short-and the long-term. Overall, BA was better in reducing symptoms in patients but this effect was not influenced by comorbid PD. Similar effects were found for a dimensional PD-measure. Only cluster-C PD-traits turned out to be associated with overall depression severity. Cluster-A PD-traits predicted poorer long-term treatment response to ADM and BA, but only on the BDI, not on the HRSD. No effects of cluster-B PD-traits were found. However, PD was associated with higher dropout. The general conclusion is that comorbid PD pathology, especially from cluster-C, is associated with higher depression severity, but not with less response to treatment. Comorbid PD did predict increased chance of dropout.