This study examines the effectiveness of a 15-session worksite coping skills intervention aimed at modifying work- and family-related risk and protective factors and at reducing negative health outcomes among mothers employed in secretarial positions. A sample of 142 mothers employed at one of four corporate worksites was assessed at pretest, immediately following the intervention, and at 6-month follow-up using multiple self-report measures. Results showed that at immediate posttest, intervention participants reported significantly lower employee role stress, higher social support from work sources, and lower levels of alcohol and tobacco use. They also tended to report less use of avoidance coping and lower psychological symptomatology. At 6-month follow-up, intervention participants reported significantly lower work-family and work environment stress, higher social support from work sources, less avoidance coping, and lower psychological symptomatology. Attrition analyses provided support for the external and internal validity of the study findings. Results were discussed in relation to issues of longitudinal prevention research and worksite-based interventions.