Background: Nondiagnostic fine-needle aspirations (FNAs) pose a dilemma in the management of patients with thyroid nodules. In most cases, these patients undergo either repeat FNA or surgical resection. However, a significant number of patients will only be observed, assuming that the risk of malignancy is low. Therefore, the purpose of this study was to determine whether the risk of malignancy is higher in patients with thyroid nodules and nondiagnostic FNAs. Methods: We reviewed reports from 4286 consecutive FNA biopsies performed on patients with thyroid nodules at our institution between 2002 and 2010. We divided FNAs into two categories: diagnostic and nondiagnostic. We collected demographic, follow-up, and pathology data from both groups and then analyzed them with analysis of variance and chi-square tests. Results: Of the 4286 FNAs, 259 were classified as nondiagnostic (6%). We saw no significant differences in age or gender between patients with diagnostic versus nondiagnostic FNAs. Of the patients with nondiagnostic FNAs, 62 underwent diagnostic thyroidectomy (24%), 74 had a repeat FNA (29%), and 123 had observation only (47%); thus, 136 patients had a cytologic or pathologic diagnosis. Patients with nondiagnostic FNAs had a significantly higher rate of all types of thyroid cancer, compared with those with diagnostic FNAs (12% versus 5%, respectively; P < 0.001). Impressively, the chance of papillary thyroid cancer was twofold higher in patients with nondiagnostic FNAs. Conclusions: The percentage of nondiagnostic FNA at our institution during this period (6%) was relatively low. However, the incidence of malignancy in these patients was significantly higher. Therefore, we recommend that patients with thyroid nodules and nondiagnostic FNAs undergo either repeat biopsy or diagnostic thyroidectomy. © 2013 Elsevier Inc. All rights reserved.