Thyroid minimally-invasive ultrasound-assisted radiofrequency ablation (RFA) may be performed under local anesthesia in ambulatory setting or under general sedation in operating room setting. Which is the most convenient approach remains controversial. A study presentend by Dr. Roberto Valcavi and Dr. Roberto Novizio during 90th Annual Meeting of the American Thyroid Association compared two series of patients treated with each method to establish rates of side effects. A group ”A” of 40 patients underwent RFA as outpatient procedure with traditional setting, receiving local pericapsular anesthesia with lidocaine plus ropivacaine, and general sedation using intravenous midazolam. A second group ”B” of 314 patients underwent RFA in operating room setting, receiving, in addition to local anesthesia and with anesthesiologic assistance, oxygen supplementation through nasal cannula and intravenous fentanyl, midazolam and propofol through a cannulated a vein. Vital parameters were monitored. Intravenous paracetamol and methylprednisolone were administered after both procedures to prevent pain and swelling. Three groups of side effects were compered between groups ”A” and ”B”: intraoperative (intense pain, intra-nodular and pericapsular bleeding, vasovagal reaction and cough), immediate postoperative (swelling, cutaneous burn and laryngeal dysfunction) and periprocedural, within 30 days (bruise, fever, pseudo-cystic transformation, nodule rupture). Data analysis was performed using SPSS v22 (IBM). To compare side effects rates between groups, chi-squared test was used. There was a statistically signiﬁcant reduction of side effects in group B (p-value <0.05) in all analysis. (group A vs group B) Intraoperative: intense pain 17.5% vs 0%; Intra-nodular bleeding 7.5 vs 0.64%; peri-capsular bleeding 2.5 vs 0.33%; vasovagal reaction 2.5% vs 0%; Cough 5% vs 1.59%. Postoperative: swelling 10% vs 0.95%, cutaneous burn 5% vs 0.33%, laryngeal dysfunction 5% vs 0.33%. Peri-procedural: bruise 5% vs 1.59%; fever 2.5% vs 0%; pseudocystic transformation 2.5% vs 0%; nodule rupture 2.5% vs 0% . Operating room management of thyroid RFA decreased the incidence of intra-operative and postoperative side effects, due to general sedation that allows physician to operate without movement interferences. The operating room cost is about 1500-3000 USD more than the cost of ambulatory setting.