The aim of this study was to define the effectiveness and safety of ultrasound(US)-guided percutaneous microwave ablation(MWA) for benign thyroid nodules with one session treatment. A total 121 benign thyroid nodules in 100 euthyroid patients underwent MWA in one medical center between August 2014 and December 2015. MWA was performed with an internally cooled antenna under local anesthesia. The volume of the nodule, cosmetic score and symptom score were compared before and after the procedure. The volume reduction rate(VRR) was also evaluated. The side effects and complications were observed. As a result, microwave ablation was associated with a significant decrease in nodule volume{1.05±1.05mL (0.08~4.33mL)vs 8.56±4.21mL(4.05~22.66mL), p <0.001} at 12-month follow-up. The largest diameter was also decreased {1.36±0.53cm(0.60~3.73cm) vs 2.94±0.55cm(2.00~4.40cm) , p<0.001}. The symptom score and cosmetic score were decreased significantly after the procedure(1.71±0.68 vs 3.31±1.13, p<0.001; 1.16±0.37 vs 2.37±0.94, p<0.001). The VRR was 57.66±22.95%, .70.23±20.07%, 85.97±14.04% at 3-, 6- and 12-month follow-up after ablation , respectively. Two patients(2.0%) experienced hoarseness and recovered within 2 months. Two patients(2.0%) developed slight burn on cervical skin. One case(1%) developed Horner Syndrome, recovered within 2 months. Ultrasound-guided percutaneous microwave ablation developed significant volume reduction on benign thyroid nodules, with achieving improvement in symptom score and cosmetic grading. The treatment was well tolerated.