Different methods to reduce blood loss during spinal surgery have been described already. Although the use of the harmonic scalpel (HS), an ultrasonically activated coagulator, has been described in endoscopic spinal surgery, its efficacy in posterior instrumentation of the spine remains unclear. The aim of this study was to determine if blood loss was lower using the HS than electrocauterization (EC) and to evaluate the cost effectiveness of the HS in reducing the need for transfusion in patients undergoing posterior instrumentation of the spine. The two groups were matched in a blinded manner, without knowledge of blood loss and were similar with respect to mean age, diagnosis and operation data. All instrumentations were done by the same surgeon. After matching was completed (HS group n = 50, EC group n = 50) blood loss and overall costs for blood products were analyzed by independent observers. The following were significantly lower with the HS than with EC: (1) blood loss (1106+/-985 ml vs 2176+/-1764 ml, P < 0.001), (2) frequency of cell saver use (13 vs 28 patients, P = 0.001), (3) average cost of blood products (Euro 72 vs Euro 219, P < 0.001), (4) predonation of autologous fresh frozen plasma (2.58+/-2.78 vs 4.5+/-2.2 U, P = 0.002) and red blood cells (0.38+/-0.75 vs 0.88+/-1.1 U, P = 0.009). The overall costs, including the costs for the HS, remained neutral. The use of the HS in posterior spinal surgery leads to significantly lower blood loss, and less need for and cost of blood products, compared to EC in cases with major anticipated blood loss.