Objective: The objective of this study was to assess the antiproliferative pleiotropic effects of statins on thyroid function, volume, and nodularity. Subjects and Methods: One hundred and six hyperlipidemic patients were included in this prospective study. The 69 patients in the statin groups received atorvastatin (16 received 10 mg and 18 received 20 mg) or rosuvastatin (20 received 10 mg and 15 received 20 mg). The 37 patients in the control group, assessed as not requiring drugs, made only lifestyle changes. Upon admission and after 6 months, all patients were evaluated by ultrasonography as well as for lipid variables (total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides) and thyroid function and structure. Results: After 6 months, no differences in thyroid function, thyroid volume, the number of thyroid nodules, or nodule size were observed in the statin and control groups. In a subgroup analysis, total thyroid volume had decreased more in patients receiving 20 mg of rosuvastatin than that in the control group (p < 0.05). Maximum nodule size had decreased more in those receiving 10 mg of rosuvastatin (p < 0.05). Conclusions: Our results suggest an association between rosuvastatin treatment and smaller thyroid volume and maximum nodule diameter; this could be attributable to the antiproliferative effects of statin therapy on the thyroid.