Objectives-To compare the adequacy of 23-, 25-, and 27-gauge needles in the fine-needle aspiration biopsy of thyroid nodules to develop guidelines for the collection of better specimens for cytologic diagnosis. Methods-This randomized prospective study included 156 consecutively enrolled patients with 156 nodules. Each nodule was aspirated with a needle of each size. The obtained specimens were analyzed independently by 2 cytopathologists, and adequacy rates were calculated. Results-In our investigation, there were no statistically significant differences among the adequacy rates achieved with 23-, 25-, and 27-gauge needles (88.5%, 90.4%, and 89.7%, respectively; P>.05). The adequacy rates achieved with all 3 needle sizes in hyperechoic nodules were higher than those in hypoechoic samples (P<.05). Finally, no differences in adequacy for the different needle sizes were observed according to nodule size (P>.05). Conclusions-We conclude that fine-needle aspiration biopsy with a 27-gauge needle can aspirate an adequate specimen for cytopathologic diagnosis of thyroid nodules. The likelihood that inadequate materials will be obtained from hypoechoic nodules is higher than that for hyperechoic nodules.