In this study, the authors examined prospectively the 24-month natural course of remission from major depressive disorder (MDD) as a function of personality disorder (PD) comorbidity. In 302 participants (196 women, 106 men), psychiatric and PDs were assessed at baseline with diagnostic interviews, and the course of MDD was assessed with the Longitudinal Interval Follow-Up Evaluation at 6-, 12-, and 24-month follow-ups. Survival analyses revealed an overall 24-month remission rate of 73.5% for MDD that differed little by gender. Participants with MDD who had certain forms of coexisting PD psychopathology (schizotypal, borderline, or avoidant) as their primary PD diagnoses had a significantly longer time to remission from MDD than did patients with MDD without any PD. These PDs emerged as robust predictors of slowed remission from MDD even when controlling for other negative prognostic predictors.