Abstract: Objective To evaluate the long-term efficacy of microwave ablation in the treatment of small renal cell carcinoma (RCC). Methods We retrospectively analyzed 140 cases of small cell renal carcinoma (151 lesions with a mean diameter of 2.8± 0.8 cm) treated between April, 2006 and October, 2015 with ultrasound-guided microwave ablation with cooled-shaft needle antenna. One microwave ablation antenna was used for tumors less than 2 cm in diameter and 2 antennas were used for larger tumors. The patients received enhanced ultrasound and CT/MRI examinations at 1, 3, and 6 months after the operation and every 6 months thereafter. The overall survival, disease-free survival, and local tumor progression rate of the patients were evaluated. Results The response rate of treatment (complete ablation at one month on enhanced images) was 100% in these patients. The local tumor progression rates at 1, 3, and 5 years were 0.9%, 2.0%, and 7.1%, respectively, and the 1-, 3-, and 5-year distant metastasis rates were 1.6%, 2.5%, and 7.9%, respectively. The overall survival rates of the patients at 1, 3, and 5 years were 98.4%, 94.8%, 89.5%, respectively, with disease-free survival rates of 98.4%, 93.0%, and 83.1%, respectively. No major complications occurred in these cases, and multivariate analysis showed that the tumor number (P=0.015) and tumor growth patterns (P=0.049) were independent risk factors that adversely affected the long-term outcome after surgery. Conclusion Our data show that microwave ablation is a safe and effective modality for treatment of renal cell carcinoma.