Objective: This study assessed whether high levels of iodide administered during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) differentially influenced thyroid function compared to PCI for non-complex coronary lesions. Subjects and Methods: A total of 615 patients were enrolled in the study; 205 underwent elective PCI for CTO lesions (Group I) and 410 underwent elective PCI for non-complex lesions including non-CTO, non-bifurcation, non-calcified, and non-tortuous lesions (Group II). Patients were monitored for development of incidental thyroid dysfunction between 1 and 6 months after PCI. Results: The patients in Group I were administered a median of 255 mL of contrast medium during PCI for CTO; a median of 80 mL was administered to the patients in Group II during non-complex PCI (p =0.001). Ten (5.4%) of the 186 euthyroid patients in Group I and 19 (5%) of the 379 eu-thyroid patients in Group II developed subclinical hyper-thyroidism (p = 0.854). However, 7 (50%) of the 14 subclinical hyperthyroid patients in Group I and only 3 (12%) of the 25 subclinical hyperthyroid patients in Group II developed overt hyperthyroidism (p = 0.019). Conclusion: In euthyroid patients, PCI for coronary CTO lesions did not increase the risk for subclinical hyperthyroidism when compared to PCI for non-complex coronary lesions. However, in patients with subclinical hyperthyroidism at baseline, PCI for coronary CTO lesions significantly increased the development of overt hyperthyroidism when compared to PCI for non-complex coronary lesions.