Purpose: To examine the potentially inappropriate prescription of thiazolidinediones (TZD). Methods: Data on TZD prescriptions were collected from Taiwan's National Health Insurance dataset from 2001 to 2006. TZDs were considered inappropriately prescribed when they were prescribed to patients who were (1) under 18 years old, (2) pregnant, who had (3) type 1 diabetes, (4) severe heart failure, (5) hepatic insufficiency, or (6) renal insufficiency and taking TZD + metformin in combination. We aggregated potentially inappropriate prescriptions of TZD for each health- care institution in each month starting from March 2001, when TZD was introduced to Taiwan's market. Results: The potentially inappropriate prescription of TZD increased from 9.41% in 2001 to 12.50% in 2006. Prior inappropriate prescription led to a 0.06% (95%CI: 0.04-0.08) further increase in its later inappropriate prescription. Accumulated months of experience prescribing TZD was found associated with higher proportion of inappropriate prescription of TZD (0.03%, 95%CI: 0.01-0.05). However, it was negatively associated with new incidence of inappropriate prescription of TZD (-0.20, 95%CI: -0.22 to -0.18). The greater the volume of prior TZD prescription (-0.87%, 95%CI: -0.93 to -0.81) and the greater the number of accumulated months since adoption (-0.14%, 95%CI: -0.16 to -0.12), the greater the decrease in rates of new inappropriate prescriptions. Conclusions: Along with the quick penetration of the new DM drug came an increased possibility that it would be prescribed inappropriately, a trend that persisted over time.