BACKGROUND Depression is a prevalent psychiatric disorder with high personal and public health consequences, partly due to a high risk of recurrence. This longitudinal study examines personality traits, structural and subjective social support dimensions as predictors of first and recurrent episodes of depression in initially non-depressed subjects. METHODS Data were obtained from the Netherlands Study of Depression and Anxiety (NESDA). 1085 respondents without a current depression or anxiety diagnosis were included. 437 respondents had a prior history of depression, 648 did not. Personality dimensions were measured with the NEO-FFI, network size, partner-status, negative and positive emotional support were measured with the Close Person Questionnaire. Logistic regression analyses (unadjusted and adjusted for clinical variables and sociodemographic variables) examined whether these psychosocial variables predict a new episode of depression at two year follow up and whether this differed among persons with or without a history of depression. RESULTS In the unadjusted analyses high extraversion (OR:.93, 95% CI (.91-.96), P<.001), agreeableness (OR:.94, 95% CI (.90-.97), P<.001), conscientiousness (OR:.93, 95% CI (.90-.96), P<.001) and a larger network size (OR:.76, 95% CI (.64-.90), P=.001) significantly reduced the risk of a new episode of depression. Only neuroticism predicted a new episode of depression in both the unadjusted (OR:1.13, 95% CI (1.10-1.15), P<.001) and adjusted analyses (OR:1.06, 95% CI (1.03-1.10), P<.001). None of the predictors predicted first or recurrent episodes of depression differently. CONCLUSIONS we used a relatively short follow up period and broad personality dimensions. CONCLUSIONS Neuroticism seems to predict both first and recurrent episodes of depression and may be suitable for screening for preventive interventions.