Objectives: The aim of this study was to compare how often fine-needle aspiration (FNA) would be recommended for nodules in unselected, low-risk adult patients referred for sonographic evaluation of thyroid nodules by ACR Thyroid Imaging Reporting and Data System (TI-RADS), the American Thyroid Association guidelines (ATA), Korean Thyroid Imaging Reporting and Data System (K-TIRADS), European Thyroid Imaging Reporting and Data System (EU-TIRADS), and Artificial Intelligence Thyroid Imaging Reporting and Data System (AI-TIRADS). Methods: Seven practices prospectively submitted thyroid ultrasound reports on adult patients to the ACR Thyroid Imaging Research Registry between October 2018 and March 2020. Data were collected about the sonographic features of each nodule using a structured reporting template with fields for the five ACR TI-RADS ultrasound categories plus maximum nodule size. The nodules were also retrospectively categorized according to criteria from ACR TI-RADS, the ATA, K-TIRADS, EU-TIRADS, and AI-TIRADS to compare FNA recommendation rates. Results: For 27,933 nodules in 12,208 patients, ACR TI-RADS recommended FNA for 8,128 nodules (29.1%, 95% confidence interval [CI] 0.286-0.296). The ATA guidelines, EU-TIRADS, K-TIRADS, and AI-TIRADS would have recommended FNA for 16,385 (58.7%, 95% CI 0.581-0.592), 10,854 (38.9%, 95% CI 0.383-0.394), 15,917 (57.0%, 95% CI 0.564-0.576), and 7,342 (26.3%, 95% CI 0.258-0.268) nodules, respectively. Recommendation for FNA on TR3 and TR4 nodules was lowest for ACR TI-RADS at 18% and 30%, respectively. ACR TI-RADS categorized more nodules as TR2, which does not require FNA. At the high suspicion level, the FNA rate was similar for all guidelines at 68.7% to 75.5%. Conclusion: ACR TI-RADS recommends 25% to 50% fewer biopsies compared with ATA, EU-TIRADS, and K-TIRADS because of differences in size thresholds and criteria for risk levels.