Objective: Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. Materials and methods: We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 +/- 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. Results: ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion: Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.