The aim of our study is a retrospective evaluation of effectiveness and safety of Computed Tomography (CT)-guided radiofrequency ablation (RFA) therapy of primary and metastatic lung lesions in patients that cannot be considered surgical candidates. From February 2007 to September 2017, we performed 264 CT-guided ablation sessions on 264 lesions in 174 patients (112 M and 62 F; mean age, 68 years; range 36-83 years) affected by primary and metastatic lung lesions. The 45% of patients was affected by primary lung cancer, with size range lesion of 10-50 mm, and the 55% by metastatic lung lesions with size range of 5-49 mm. All patients had no more than three metastases in the lung and pulmonary relapses were treated up to three times. Overall Survival (OS), Progression-Free Survival (PFS), Local Progression-Free Survival (LPFS) and Cancer-specific survival (CSS) at 1, 3 and 5 years were calculated both in primary lung tumors and in metastatic patients. Immediate and late RFA-related complications were reported. Pulmonary function tests were evaluated after the procedures. The effectiveness of RFA treatment was evaluated by contrast-enhanced CT. In patients affected by primary lung lesions, the OS rates were 66.73% at 1 year, 23.13% at 3 years and 16.19% at 5 years. In patients affected by metastatic lung lesions, the OS rates were 85.11%, 48.86% and 43.33%, respectively, at 1, 3 and 5 years. PFS at 1, 3 and 5 years were 79.8%, 60.42%, 15.4% in primary lung tumors and 78.59%, 51.8% and 6.07% in metastatic patients. LPFS at 1, 3 and 5 years were 79.8%, 64.69%, 18.87% in primary lung tumors and 86.29%, 69.15% and 44.45% in metastatic patients. CSS at 1, 3 and 5 years was 95.56%, 71.84%, 56.72% in primary lung tumors and 94.07%, 71% and 71% in metastatic patients. Immediate RFA-related complications (pneumothorax, pleural effusion and subcutaneous emphysema) were observed, respectively, in 42, 53 and 13 of 264 procedures (15.9%, 20% and 5%). There also occurred one major complication (lung abscess, 0.36%). No significant worsening of pulmonary function was noted. Our retrospective evaluation showed long-term effectiveness, safety and imaging features of CT-guided RFA in patients affected by primary and metastatic lung cancer as an alternative therapy in non-surgical candidates.