OBJECTIVES: To compare the medication adherence and persistence of existing users of chronic medications enrolled in a pharmacy chain's appointment-based medication synchronization (ABMS) program, with patients who are not enrolled in the program for the duration of one year. METHODS: A retrospective cohort study compared patients receiving ABMS with matched controls receiving usual standard care. ABMS consisted of an appointment to synchronize the patient's medications to be dispensed on a single appointment day every month, a call to the patient prior to the appointment day to address any prescription changes and to remind the patient, and a patient visit to the pharmacy to pick up the medication. Outcomes measured were 1-year adherence rates using proportion of days covered (PDC) and 1-year non-persistence rates. Data for this study came from prescription claims records of patients taking one of six chronic medication classes during the period of December 1, 2011 to February 28, 2014. ABMS patients were matched with controls on prior adherence behavior, medication class, age, gender, and geographic region. RESULTS: Mean PDC scores ranged from 0.73 to 0.91 for ABMS patients, and from 0.57 to 0.71 for controls depending on the medication class. The percentage of adherent individuals (i.e., PDC≥ 0.8) was 55% to 84% for ABMS participants and 37% to 62% for controls. Odds of adherence was 2.3 to 3.6 times greater with ABMS. Controls became non-persistent (61% to 74%) more often than ABMS patients (33% to 44%) with hazard ratios of non-persistence being 0.39 to 0.67 for individuals in the program. Compared to controls, study patients had a 33% to 61% lower likelihood of non-persistence, depending on the drug class. CONCLUSIONS: ABMS program in a community pharmacy setting was associated with significant improvements in adherence and persistence for patients who were existing users of chronic medications for at least six months.