OBJECTIVES: To evaluate the impact of an automated prescription refill intervention program on medication adherence. METHODS: A retrospective pre-post with case and control cohort study design was employed using a large administrative pharmacy claim database. An automated prescription refill program was implemented in January 2009 across five pharmacy stores. Patients who filled at least one maintenance medication during January of 2009 in either of five pre-identified test or five pre-identified control pharmacy retail stores were included in the test or control groups. Individual patients’ 6-months pre and 6-months post adherence was compared by measuring mean Medication Possession Ratio (MPR). Relationship between Autorefill program and medication adherence was investigated by linear regression models. RESULTS: A total of 14,904 patient records from test group and 26,911 patient records from control group were identified and included in the study. Mean age for test group was higher than control group patients (60 vs 55). Both groups had similar gender distribution (Females-Test 60.5% vs 60.4% control). Mean MPR for test group was found to be higher than control group (68% vs 60%). After controlling for demographic factors and pre-index MPRs, test group showed a significant 4% increase in the mean MPR as compared to the control group patients (p<0.05). Drill-down analyses were conducted across top five therapeutic classes including antihypertensives, antihyperlipicemics, antidepressants, contraceptives, and antidiabetics. Test group patients for all classes except antihypertensive and contraceptive agents reported significantly higher mean MPR than control group patients (p<0.05). Test patients using antihypertensive or contraceptive agents showed a higher mean MPR as compared to control group patients, however, those differences were not found to be statistically significant. CONCLUSIONS: Study findings suggest that automated prescription refill intervention program may have had a positive impact on patients’ adherence, especially in patients who were filling their antihyperlipidemic, antidepressant or antidiabetic medications.