OBJECTIVES: To assess efficacy, safety and cost-effectiveness of ultrasonic dissector, Harmonic Scalpel (HS) versus conventional non video-assisted thyroidectomy (nHS), from hospital and societal perspectives. METHODS: A total of 198 patients eligible for total thyroidectomy (TT) were randomly assigned to surgery with HS(96) or nHS(102) and followed until 3 months after discharge. Main clinical outcomes were: pain (VAS score), QoL (EQ-5D), complications, cosmetic results. Direct medical and indirect costs were prospectively collected as well. RESULTS: HS led to shorter operative time (HS:54.16 vs nHS:76.36 minutes, P<0.001), as total operative room (OR) occupation time (76.86 vs 100.59 minutes, P<0.001). QoL was better in HS-group one month (0.90 vs 0.83 ; P<0.002), and 3 months after surgery (0.91 vs 0.84; P=0,002). Less postoperative pain was perceived by HS patients 6 hour after surgery (HS: 41.35 vs nHS: 44.56) but similar after 48 hours (HS: 22.75 vs nHS:20.97). A total of 71% HS patients were satisfied with cosmetic result versus 55% nHS (P=0.029). No significant difference resulted in complications rate and voice changes. Total medical direct costs were €2400.34 and €2540.52 for HS and nHS, respectively. From hospital perspective HS offers a cost saving of € 119/patient, mainly due to less charges of OR personnel (HS: €294.19 vs nHS: €452.90), OR occupancy (HS: €620.61 vs nHS: €815.40), drugs (HS: €63.29 vs nHS: €93.28), and diagnostic exams (HS: €132.91 vs nHS: €160.36). No statistical difference was found in loss of productivity up to 3 months (HS: €385.51 vs nHS: €377.71). CONCLUSIONS: Harmonic is safe and efficacious in conventional TT, allowing a significant reduction of the operative time (-22 min), total OR occupation time (-24 min), and better QALY at 3 months (HS:0,23 vs nHS:0,21), without increasing complications rate and saving €119 from a hospital perspective. Harmonic should be adopted in TT to reduce impact on individual life and on society.