OBJECTIVES: To establish a framework assessing effects of multiple drug switching patterns, this preliminary study aimed to assess the risk of cardiovascular diseases (CVDs) associated with antidiabetic monotherapy intervals in type-2 diabetic (T2D) patients. METHODS: This retrospective cohort study was conducted from April 2004 to February 2009 using the Taiwan Pay-for-Performance Diabetes Registry (November 2003 to February 2009), which contains clinical indicators and claim records of registered diabetic patients. Adult newly-registered T2D patients who initiated antidiabetics from April 2004 to February 2009 were included. Individuals’ antidiabetic monotherapy intervals including metformin, sulphonylureas (SUs), meglitinides (MGs), acarbose, pioglitazone, rosiglitazone, and insulin were identified and followed to any change of interval, cardiovascular event (i.e. myocardial infarction, ischemic heart disease and congestive heart failure) or the end of study. Cox regression was used to evaluate CVD risk associated with different interval groups comparing against metformin and adjusted for diabetic history (year), gender, age, body mass index, blood pressure, triglyceride, and use of anti-hypertensive and lipid-controlling drugs. RESULTS: Of the 75,303 newly-registered T2D patients without CVDs included in the study, 150,144 intervals and 949 events were identified. The mean follow-up duration was 3.9±2.1 years per patient and the mean interval period was 238±317 days. Of the seven interval groups, SU monotherapy was the most frequently identified and the highest CVD incidence group. All interval groups had significantly higher risk of CVDs than metformin, the Hazard Ratio (95% confidence interval) for SUs, MGs, acarbose, pioglitazone, rosiglitazone, and insulin were  1.563 (1.31, 1.86); 1.38 (1.10, 1.74); 1.56 (1.22, 1.98); 1.53 (1.19, 1.95); 1.50 (1.18, 1.92); 1.48 (1.20, 1.83), respectively. CONCLUSIONS: The results are inconsistent with previous literature comparing CVD risk of acarbose, MGs and pioglitazone against metformin. Interval-based CVD risk may be biased by the interval definition (monotherapy, multiple-therapy, multiple switching) and individual patients’ underline condition.