Objective To explore the effect of microwave ablation on the specimen quality, risk of bleeding and histopathological outcomes of core needle biopsy in thyroid nodules. Methods Core needle biopsy were performed on 251 cases of thyroid solitary nodules before and after microwave ablation, and then the specimen quality, hemorrhage of thyroid nodules after biopsy, legibility of pathological slices and the consistency of pathological diagnosis were compared. Results The specimen satisfaction rate of thyroid nodules after microwave ablation was significantly improved compared with that before microwave ablation (100%[251/251] vs 92.03%[231/251], P=0.000), and the incidence of bleeding after microwave ablation was significantly decreased versus that before microwave ablation (0% vs 15.14%[38/251]; P=0.000). And 184 of 251 thyroid nodules were benign and 67 were papillary thyroid carcinoma. In addition to 4 thyroid nodules which could not be sliced due to poor quality before microwave ablation, the overall consistency of pathological diagnosis in the remaining nodules before and after microwave ablation was 100%. Conclusion Core needle biopsy immediately after microwave ablation does not affect the diagnostic accuracy of thyroid nodules, and can reduce the risk of bleeding and improve the specimen quality.