Background: Previous studies have shown that work-privacy conflict (WPC) can have detrimental effects on mental and physical health, interpersonal relationships, and family functioning. However, these detrimental effects vary widely between individuals. At the same time, there is evidence that the Big Five personality traits interact with how people cope with stress and conflict, so they may partly explain these differences. Thus, this study aims to examine the moderating role of the Big Five personality traits in the association between WPC and relationship satisfaction in mothers and fathers. Methods: Data from 686 mothers and 702 fathers were derived from a longitudinal cohort study from Eastern Germany. Established questionnaires were used to measure personality at eight weeks, WPC at 14 months, and relationship satisfaction at two years after childbirth. Hierarchical linear regression analyses were performed including relevant confounding variables. Results: WPC alone did not predict maternal relationship satisfaction, whereas it significantly interacted with neuroticism. Mothers with average and high neuroticism levels showed consistently low relationship satisfaction, irrespective of their perceived WPC. Mothers with low neuroticism levels had low relationship satisfaction when their WPC was high. For fathers, WPC alone significantly negatively predicted relationship satisfaction, yet there was no significant interaction effect with personality. Conclusions: The present findings indicate a complex interplay between WPC, neuroticism, and relationship satisfaction in mothers, including that average or high neuroticism scores alone are a potential risk factor for relationship satisfaction. Additionally, our results suggest that WPC may have a detrimental effect on relationship satisfaction in fathers, regardless of their personality traits. Based on our results we recommend developing and expanding measures related to work-family benefits to ensure balance between both domains. We also suggest prevention and intervention in the field of positive psychology.