Objective: In recent years, spectral Doppler has become a valuable diagnostic tool for assessing suspected thyroid nodules. The aim of this study was to assess the clinical use of spectral Doppler in managing thyroid nodules. Materials and Methods: This prospective cohort study included 153 patients who underwent thyroid nodule evaluation, using sonography. Peak systolic velocity, end-diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) were measured, within the suspected lesions. Results: Among the 209 identified thyroid nodules, 193 (92%) were benign and 16 (7.6%) were malignant. The RI and PI values of malignant nodules were significantly higher than measured within benign nodules. There was also a significant difference in the EDV between benign and malignant nodules ( P = .012). The RI had the highest diagnostic accuracy, with an area under the receiver operating characteristic, area under the curve, of 0.839 (95% confidence interval, 0.748–0.930). The optimal cutoff value for RI was 0.73. The results indicate that the RI with an odds ratio (OR) of 2.64, in the univariate analysis, and an OR of 2.31, in the multivariate analysis, might be successful in predicting a malignant thyroid nodule. Conclusion: This cohort study demonstrated a high sensitivity and specificity for RI and PI as predictors of malignancy in thyroid nodules, with diagnostic cutoff points of 0.73 and 1.37, respectively.