Purpose. To examine the association between multiple dimensions of work-family spill-over, and physical and mental health among working midlife adults. Design. Cross-sectional analyses of self-reported data. Setting. The National Survey of Midlife Development in the United States (MIDUS), 1995. Subjects. Employed adults aged 35-65 years (n = 1547) who participated in the telephone interview and returned the mail-back questionnaires of the MIDUS (overall response rate of 60.8%). Measures. Independent variables included negative spillover from work to family, positive spillover from work to family, negative spillover from family to work, positive spillover from family to work. Self-rated physical health, chronic conditions, obesity, self-rated mental health, negative psychological well-being, and positive psychological well-being were outcomes. Results. Independent of negative spillover between work and family, more positive spillover from work to family was associated with better physical health (odds ratio [OR] = 1.17 p less than or equal to .05) and mental health (OR = 1.28 p less than or equal to .01). More positive spillover from family to work was associated with less chronic conditions (OR = .85, p less than or equal to .05), less negative well-being (OR = .67, p less than or equal to .001), as well as better mental health (OR = 1.45, p less than or equal to .01) and more positive well-being (OR 1.76 p less than or equal to 001). Conclusions. Health promotion or employment programs and policies may need to focus on minimizing negative spillover between work and family and promoting positive spillover between work and family.