OBJECTIVES: To evaluate the persistence rate and adherence level of new oral antidiabetics (OAD) users as well as their relation to patients’ demographic and clinical characteristics. METHODS: A cohort of 160,231 patients was built from prescription records in the Régie de l’assurance maladie du Québec administrative database. All patients aged 45-85 years old who received at least one OAD prescription between January 2000 and October 2009 were included. New users were defined as having no OAD prescribed in the 2 years preceding cohort entry. The cohort entry was defined by the date of the first OAD prescription.  Persistence rate was defined by allowing a 50% grace period for renewal. Drug adherence level was estimated using MPR. The cumulative persistence rate was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of ceasing OAD after adjustment. Logistic regression models were used to establish the relation between non-adherence level and their determinants. RESULTS: Patients had a mean age of 67 years, 49% were men, 52% had a cardiovascular disease, 78% had hypertension and 59% had dyslipidemia. Persistence decreased to 51% after 1 year but the proportion of patients who refilled an OAD during the year after cessation ranged from 73 to 91%. Adherent patients (MPR ≥ 80%) accounted for 67% after 1 year. Hypertension (0.84-0.87), dyslipidemia (0.85-0.88) and cerebrovascular disease (0.89-0.99) were associated with higher persistence rates, whereas microvascular risk factors such as urologic procedure (1.01-1.17) and viral infectious diseases (1.09-1.27) demonstrated lower rates. Similar results were observed for adherence. CONCLUSIONS:  Barriers to persistence rate and adherence level occur early in the course of OAD therapy.  Adherence is a key factor in determining the success of various therapeutic approaches, thus greater attention should be paid to this aspect which may result in improved patient outcome.