Theoretical models of the antecedents and outcomes of work-home interference (WHI) suggest that work characteristics (e.g., job stressors, working hours) increase the probability that an individual experiences work-home interference. Since work-home interference is considered as a role stressor, these experiences should be detrimental for long-term well-being. In this 2-wave panel study, the authors compared this suggested pathway with competing models that propose reverse causation and reciprocal effects in a sample of 365 employees (N at T2 = 130) from the German workforce using structural equation modeling. In particular, a model with two proposed antecedents (job stressors, working hours) of WHI and two proposed consequences (depression, turnover motivation) was analyzed in alternative configurations. The results support a cyclical model with a job stressors → depression → WHI → job stressors pathway. Furthermore, working hours affected WHI, and turnover motivation emerged as an outcome of WHI.