Background Identifying depressive subtypes is an important tool in reducing the heterogeneity of major depressive disorder. However, few studies have examined the stability of putative subtypes of depression over time. Method The sample included 488 persons from the Netherlands Study of Depression and Anxiety (NESDA) who had major depressive disorder at baseline and at the 2-year follow-up assessment. A latent transition analysis (LTA) was applied to examine the stability of depressive subtypes across time-points. Differences in demographic, clinical, psychosocial and health correlates between subtypes were evaluated in a subsample of persons with stable subtypes. Results Three subtypes were identified at each time-point: A moderate subtype (prevalence T0 39%, T1 42%), a severe typical subtype (T0 30%, T1 25%), and a severe atypical subtype (T0 31%, T1 34%). The LTA showed 76% stability across the 2-year follow-up, with the greatest stability in the severe atypical class (79%). Analyses of correlates in the stable subtypes showed a predominance of women and more overweight and obesity in the severe atypical subtype, and a greater number of negative life events and higher neuroticism and functioning scores in the severe typical subtype. Conclusions Subtypes of major depressive disorder were found to be stable across a 2-year follow-up and to have distinct determinants, supporting the notion that the identified subtypes are clinically meaningful. © 2012 Cambridge University Press.