Background: The personality dimensions neuroticism and extraversion likely represent part of the vulnerability to depression. The stability over longer time periods of these personality dimensions in depressed patients treated with psychological treatment or medication and in untreated persons with depression in the general population remains unclear. Stability of neuroticism and extraversion in treated and untreated depressed persons would suggest that part of the vulnerability to depression remains stable over time. The current study addressed the question whether treatment in depressed patients is related to changes in neuroticism and extraversion. Methods: Data are from 709 patients with major depressive disorder participating in a cohort study (Netherlands Study of Depression and Anxiety; NESDA). We determined the 2-year stability of extraversion and neuroticism in treated and untreated persons and related change in depression severity to change in personality over time. Results: Neuroticism decreased from baseline to 2-year follow-up (d = 0.73) in both treated and untreated persons. Extraversion did not change significantly after controlling for neuroticism and depression severity at baseline and follow-up. Decreased depressive symptoms over time were related to decreased neuroticism (d = 1.91) whereas increased depressive symptoms over time were unrelated to neuroticism (d = 0.06). Limitations: Patients were not randomized to treatment conditions and the groups are therefore not directly comparable. Conclusions: Treated patients with depression in the general population improve just as much on depression severity and neuroticism as untreated persons with depression. This suggests that changes in neuroticism in the context of treatment likely represent mood-state effects rather than direct effects of treatment.