The Harmonic Scalpel (HS) is frequently used for hepatic resection. Yet, no current study addresses its utility compared to conventional methods. We reviewed our experience with this device to determine if it decreased perioperative complications when compared to the traditional clamp crushing technique. One hundred forty-nine anatomic hepatic resections were performed at our institution from September 1992 to February 2002. Patients were divided into two groups based on the technique of resection: HS [53% (n = 79)] versus clamp crushing [47% (n = 70)]. Use of the HS was associated with a shorter mean operative time (357 +/- 15.0 vs. 404 +/- 19.1 min; p = 0.05) and a trend toward decreased blood loss (1211 +/- 125.5 vs. 1411 +/- 180.7 mL; P = NS) and transfusion requirements (2.6 +/- 0.5 vs. 1.7 +/- 0.3 units; P = 0.10). However, use of the HS was associated with a significant increase in biliary fistulas [24% (n = 19) vs. 7% (n = 5); P = 0.01]. Use of the Harmonic Scalpel was associated with decreased operative time and a trend toward decreased blood loss and transfusion requirements. Its use was also associated with a significant increase in the incidence of postoperative bile leaks, and, therefore, surgeons must be vigilant during liver parenchymal transection when using this device.