Objective: To evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) for small renal masses (SRMs) at a large single-institution center during a period of 12 years. Materials and methods: A total of 118 patients underwent RFA for SRM between July 2006 and July 2018 at our institution. We included demographic information, comorbidity, procedural details, and oncological outcome in the analysis. Survival analysis was performed using competing risk. Results: 87 males and 31 females with median age 66 years underwent RFA. Median tumor size was 23 mm. Tumor biopsy was performed in 94% of cases, of which 56% were confirmed renal cell carcinoma (RCCs). Twenty-eight patients had benign tumors or underwent treatment for recurrence of prior RCC. Median follow-up of 5 years. Median Charlson Comorbidity Index was 5. Major complications occurred in 1.7%. No change in kidney function was observed. The initial treatment response was 98%. Among patients treated for newly diagnosed radiological suspected RCC without Von Hippel-Lindau or benign biopsy (90 pts), the cumulative incidence of radiological recurrence after 5 and 10 years was 6.6% (95% CI: 0.8–12%) and 16% (95% CI: 4.2–28%), respectively. Three patients died of RCC during follow-up. The cumulative incidence of kidney cancer death was 4.5% (95% CI: 4.3–13%) after 10 years. The incidence of other-cause mortality was 50% (95% CI: 34–67%). Conclusion: CT-guided RFA is a safe and effective treatment option for patients unsuitable for surgery. RFA is a good alternative to partial or radical nephrectomy for SRMs, although randomized trials comparing surgery to minimally invasive thermal ablation techniques are missing.