This study aimed to compare the diagnostic performance of core-needle biopsy (CNB) to fine-needle aspiration (FNA) as a first-line diagnostic tool in initially detected thyroid nodules, according to ultrasound (US) patterns.This study included 778 consecutive nodules from 705 patients who underwent CNB from one institution and 627 nodules from 583 patients who underwent FNA from two institutions. Adjustments for significant differences in patients' characteristics were facilitated via propensity score matching. We compared the diagnostic performance of CNB and FNA for thyroid malignancy according to three diagnostic criteria for all nodules and the US patterns.A 1:1 matching of 469 patients yielded no significant differences between CNB and FNA for any covariates. CNB showed a significantly higher sensitivity for malignancy than FNA with any criterion (criterion 1: category VI, criterion 2: category V and VI, criterion 3: category IV, V and VI) in overall and high suspicion nodules (90.1-99.5 % vs. 69.7-88.3 %, all P-values < 0.001) and low/intermediate suspicion nodules, except criterion 1 (61.9-100 % vs. 36.4-45.5 %, all P ≤ 0.016). In ROC curve analysis, the AUCs of CNB were significantly higher than those for FNA with any criterion in overall and high suspicion nodules (P < 0.001) and in low/intermediate suspicion nodules, except criterion 1 (P ≤ 0.008). CNB had a slightly higher minor complication rate than FNA (0.7 % vs. 0%, P ≥ 0.069).Our study suggests that CNB has a complementary role as an alternative first-line diagnostic tool to FNA for the initial diagnosis of thyroid nodules when performed by an experienced operator.