ABSTRACT Demands and stressors from work increasingly encroach upon people’s family lives in modern settings, resulting in poorer familial relationships and impaired psychological health. The current study proposed and examined dispositional optimism as a potential psychological buffer of the deleterious impact of negative work-to-family spillover (WFS) on psychological health. Based on a sample of employed midlife adults in the United States (N = 1,252) drawn from a large and nationally representative dataset, MIDUS 3, we found that dispositional optimism significantly moderated the relationship between negative WFS and subjective well-being, even after controlling for a variety of potential confounds. However, this moderation effect was not consistently observed for the relationship between negative WFS and depressive symptoms, suggesting that the buffering utility of dispositional optimism may be limited to day-to-day subjective well-being and may not extend to the domain of mental health issues. Nonetheless, our findings indicate the potential importance of considering psychological resources in our efforts to mitigate strains on psychological health arising from negative WFS – to which future studies are encouraged to explore further.