Using ecological theory as a theoretical framework, this study systematically examined the associations between multiple dimensions of family relationship quality, work characteristics, work-family spillover, and problem drinking among a national sample of employed, midlife adults (n= 1,547). Multivariate analyses confirmed that work and family microsystem factors were associated with problem drinking above and beyond individual characteristics. Consistent with previous research, results indicated that a higher level of marital disagreement and more work-related pressure were associated with higher odds of problem drinking. Results also indicated that a higher level of positive spillover from family to work was associated with lower odds of problem drinking, whereas a higher level of positive spillover from work to family was associated with higher odds of problem drinking. Psychological well-being did not account for the association between work and family factors and problem drinking. Associations were similar for men and women.