The aim of this study was to assess the adequacy and efficacy of ultrasonography (US)-guided fine-needle aspiration cytology (US-FNAC) with one-sampling technique (only one specimen through a single needle pass was obtained during the procedure on each thyroid nodule in each study patient) for the cytological diagnosis of thyroid nodules. In this study, US-FNAC techniques, including "free two-hand," "mixed sampling," "flipping-extraction," and "single-needle-pass" procedures were used to collect thyroid cells from July 2007 to June 2009. The cytopathology results and patients' complications were reviewed retrospectively. Of the 1456 thyroid-nodule samples obtained from 977 patients (1.49 per patient), the incidence of adequate and inadequate samplings was 88.5% (1289/1456) and 11.5% (167/1456), respectively. After thyroid surgery in 396 patients, 568 nodules were confirmed as 353 papillary thyroid carcinomas including one diffuse sclerosing variant, five follicular thyroid carcinomas, three medullary thyroid carcinomas, one anaplastic thyroid carcinoma, one metastatic renal cell carcinoma, two poorly differentiated carcinomas, 17 follicular adenomas, two nodular thyroiditis, two pseudonodules related to thyroiditis, and 182 cases of nodular hyperplasia. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false-negative rate, and false-positive rate for the US-FNAC were 94.3%, 91.9%, 96.2%, 88.3%, 93.6%, 3.9%, and 2.6%, respectively. There were no significant patients' complications, but 87 patients (8.9%) reported mild pain during or after the procedure. This study showed a good adequacy and efficacy of US-FNAC for thyroid nodules despite one-sampling.