BACKGROUND: Prior research suggests that the Big Five personality dimensions might be associated with coping strategies as well as acute psychopathology. The aim of the present study was to investigate direct and indirect associations between the Big Five personality traits, coping styles, and psychopathological variables. SUBJECTS AND METHODS: Subjects were 1140 adults from various institutions and regions in Hungary. A comprehensive test battery was administered including the Big Five Inventory (BFI), Psychological Immune System Inventory (PISI), and some subscales of the Brief Symptom Inventory (BSI). Several moderation-mediation analyses were conducted using the PROCESS tool in SPSS to test for influence paths. RESULTS: Coping and personality variables jointly accounted for 40% to 50% of variance in psychopathology outcome. Personality dimensions of Extraversion, Conscientiousness and Emotional Stability had strongest predictive values. Emotional Stability had a more direct and unmediated effect, whereas Extraversion and Conscientiousness effects were mediated by the Approach and Self-regulation coping systems. In comparison to personality, coping style was generally a stronger predictor. CONCLUSIONS: The findings of this study might add to better understanding of complex pathways leading from broad personality dimensions to coping strategies and psychological (mal)adjustment