OBJECTIVES: According to the Centers for Disease Control, nearly twenty percent of the American workforce has some type of mental disorder. Depression is especially prevalent, and antidepressant use in the United States. is common; today, one in ten Americans over the age of 12 takes an antidepressant medication. This study assesses the relationships between antidepressant medication adherence and short-term disability costs in a large manufacturing company.   METHODS: A retrospective analysis of pharmacy claims was conducted to identify individuals within a large manufacturing company who were continuously eligible for a three-year time frame (between 2001 - 2007) and who received a prescription for an antidepressant during that time. In those cases where an individual’s eligibility spanned a longer time period, the most recent three-year span was chosen. The resulting sample included both treatment-naïve and treatment-experienced patients. Medical, pharmacy, and short-term disability costs were calculated for a one year follow-up. Adherence was measured using proportion of days covered (PDC), where a PDC≥80 was considered adherent.  Multi-variable linear regression was used to examine the relationships between cost and adherence, controlling for patient demographics (age, gender, and job type) and Charlson co-morbidity score.  RESULTS: Among the 14,737 individuals in the study, the mean adherence to antidepressants was 49%, and 28% (N=4178) of the study population had a PDC≥80. The average total medical/pharmacy costs were higher for the adherent patients. Individuals who were adherent to their antidepressant medications, howwever, had lower short-term disability costs ($2129/year) than did the non-adherent ($2440/year).  CONCLUSIONS: In general, patients who were adherent to their antidepressant regimens had lower short-term disability costs than did the non-adherent. Employers concerned with the impact of depression on their employee costs should pay particular attention to this association between antidepressant adherence and short-term disability.