OBJECTIVES: To evaluate the impact of Food and Drug Administration (FDA) safety warning on the utilization rates of thiazolidinedione oral anti-diabetes medications using an interrupted time series analysis.  METHODS: The analysis used data from the five percent national sample of Medicare Part D beneficiaries.  Beneficiaries were included if they were diabetic, continuously enrolled in Part D and had filled a prescription for a thiazolidinedione medication at any time during the period of January 2006 through December 2008. Beneficiaries were classified each month into appropriate-use, at risk, and contraindicated groups based on the presence of certain comorbid conditions. Data were aggregated to monthly utilization rates. Analyses examined the effects of the May 2007 FDA safety warnings about the ongoing review of rosiglitazone’s potential to increase cardiovascular risks on thiazolidinedione utilization rates for the different appropriateness of use categories using an interrupted time series consisting of 32 data points (13 months before and 19 months after the safety warning).  RESULTS: There was an increasing trend in the total utilization rates of thiazolidinediones before the safety warning. Significant decline in drug utilization rates were observed at the end of the study period for all patient groups on rosiglitazone (relative difference -74.78%, -79.93%, and -90.21% in appropriate-use, at risk and contraindicated patient groups, respectively). The intervention did not have significant immediate effects on the post-intervention utilization rates of pioglitazone. However, after the intervention, a general decline in utilization of thiazolidinediones, including pioglitazone, was observed. CONCLUSIONS: The initial safety warning about rosiglitazone’s cardiovascular safety was effective in decreasing rosiglitazone’s utilization in the targeted population and thus appeared to achieve the desired safety effects.  The safety warning, however, also had spillover effects by reducing utilization of drugs in other patient cohorts not targeted by the warning.