OBJECTIVES To investigate the influence of member copayment differential between generic and preferred brand name prescription drugs on generic fill rate (GFR) within two drug therapy classes (antidepressants and antihypertensive). METHODS This study was a retrospective observational cohort study using individual member as the unit of analysis. The antidepressant cohort was members who utilized an antidepressant (SSRI or SNRI). The antihypertensive cohort was members who had an antihypertensive claim (ACEI, ARBs, CCB, BB, and diuretics).All 2006 claims were analyzed and adjusted to 30-day equivalents. A total of 149,359 members with age ≥ 22 years, continuously enrolled, no benefit change, with a flat copayment commercial benefit plan, and had at least one claim were eligible for analysis. Medical claims were used to calculate Charlson severity of illness scores. A Tobit model to assess the influence of independent variables: copayment differentials, age, gender, income, generic copayment, number of unique medications taken, mail-order service use, specialty drug use, other maintenance drug use, Charlson score, on the GFR (dependent variable) was built for each cohort. RESULTS Of 149,359 members, the antidepressant cohort comprised 22,484 (15.1%) members with an average 5.7 30-day antidepressant claims, mean $16.40 copayment differential, and GFR of 51.8%. For the antihypertensive cohort 33,673 (22.5%) members had 8.6 antihypertensive 30-day claims, mean $16.50 copayment differential, and GFR of 72.3%. Antidepressant Tobit model found the mean marginal effect of copayment differential on GFR was 0.005 (p<0.001) indicating a $10 copayment differential increase is estimated to increase antidepressant GFR by 5% points. In the antihypertensive cohort, the mean marginal effect of copayment differential on GFR was 0.001 (p<0.001). When copayment differential increased by $10 the estimated GFR increased by 1% point. CONCLUSIONS There was a significant positive relationship between copayment differential and generic fill rate. However, the magnitude of the effect varied across different drug therapy classes.