Objective: We aimed to clarify the influence of ThinPrep preparation, nodule size and guidance mode on the accuracy of thyroid fine-needle aspiration (FNA). Methods: A total of 1,240 thyroid FNAs were reviewed and 489 cases with histological correlations were enrolled in this study. Results: Of the 489 total cases examined, 101 were processed with both ThinPrep and conventional preparation and 388 entirely with ThinPrep. The overall nondiagnostic rate, sensitivity and accuracy of FNA were 2.0, 91.0 and 89.4%, respectively. The cases with a preoperative ultrasound (n = 469) were grouped according to nodule size. The nondiagnostic rate, sensitivity and accuracy of FNA did not differ significantly with nodule size (p1 = 0.339, p2 = 0.179, p3 = 0.119). A total of 101 resections were performed with palpation-guided FNA and 388 were performed with ultrasound-guided FNA. The nondiagnostic rates, sensitivity and accuracy of FNA were similar in these two groups. Conclusions: The ThinPrep technique is a valid method for thyroid FNA and is effective for thyroid nodules ≥0.5 cm. The reliability of FNA results is not reduced with larger nodules. The use of palpation-guided FNA for palpable solid nodules is also effective.