The aim of the study was to assess the safety and efficacy of CT-guided percutaneous radiofrequency (RF) ablation of osteoid osteoma (OO). From 1997 to 2001, RF ablation was performed on 38 patients with OO, diagnosed clinically and by radiography, scintigraphy, contrast-enhanced MRI, and CT. Treatment was performed via percutaneous (n=29) or surgical (n=9) access, under CT guidance in all cases, with an 18-gauge straight electrode. Patients were discharged within 24 h and followed up clinically (at 1 week and every 6-12 months) and with MRI (at 6 months) and scintigraphy (after 1 year). The technical success rate was 100%. Complications occurred in two patients, consisting in local skin burns. The follow-up range was 12-66 months (mean ± SD, 35.5±7.5 months). Prompt pain relief and return to normal activities were observed in 30 of 38 patients. Persistent pain occurred in eight patients; two patients refused further RF ablation and were treated surgically; RF ablation was repeated in six cases achieving successful results in five. One patient reported residual pain and is being evaluated for surgical excision. Primary and secondary clinical success rates were 78.9 (30/38 patients) and 97% (35/36 patients), respectively. CT-guided RF ablation of OO is safe and effective. Persistent lesions can be effectively re-treated. Several imaging modalities are needed for the diagnosis of OO and for the follow-up after treatment, particularly in patients with persistent symptoms.