Objectives: To compare the mechanical and clinical performance of new and reprocessed harmonic scalpels (HS). Methods: A total of 89 reprocessed and 90 new HS (laparoscopic coagulating shears with a curved blade and 5-mm-diameter shaft) were subjected to visual inspection, destructive testing, and nondestructive mechanical testing. Subsequently, new HS, randomly selected reprocessed HS, and selected reprocessed HS with known abnormalities were graded on clinical performance by 14 surgeons in a porcine model. Results: Visual inspection of the HS discriminated between the new and reprocessed instruments in 11 of the 12 visual criteria (P ≤0.02). In vitro mechanical testing revealed greater clamp arm dislodge forces for the new HS (P <0.01) and greater midshaft temperatures for reprocessed HS (P <0.01). Overall, 65 (73%) of 89 reprocessed and 7 (7.8%) of 90 new HS had gross abnormalities noted on inspection and mechanical evaluation (P <0.01). The surgeons' evaluation of the instruments during in vivo testing demonstrated that the new instruments manifested significantly greater hemostatic control compared with randomly selected reprocessed HS (P = 0.01) and were significantly better for tissue sticking (P = 0.01), tissue transection (P = 0.02), tissue dissection (P <0.01), grasping (P <0.01), and hemostatic control (P = 0.04) compared with reprocessed HS with obvious defects. Conclusions: In vitro and in vivo data demonstrated significantly greater performance for new HS compared with reprocessed HS. Mechanical testing of reprocessed HS could not adequately distinguish which HS would result in decreased performance. These findings raise important issues of clinical safety in the contemporary quest for cost-effectiveness.