Background: Liver surgery can be difficult because there are few external landmarks defining hepatic anatomy and because the liver has significant vascularity. Although preoperative tomographic imaging (computed tomography or magnetic resonance imaging) provides essential anatomical information for operative planning, at present it cannot be used actively for precise localization during surgery. Interactive image-guided surgery involves the simultaneous real-time display of intraoperative instrument location on preoperative images (computed or positron-emission tomography or magnetic resonance imaging). Interactive image-guided surgery has been described for tumor localization in the brain (frameless stereotactic surgery) and allows for interactive use of preoperative images during resections or biopsies. Hypothesis: The application of interactive image- guided surgery (IIGS) is feasible for hepatic procedures from a biomedical engineering standpoint. Methods: We developed an interactive image-guided surgery system for liver surgery and tested a porcine liver model for tracking liver motion during insufflation; liver motion during respiration in open procedures in patients undergoing hepatic resection; and tracking accuracy of general surgical instruments, including a laparoscope and an ultrasound probe. Results: Liver motion due to insufflation can be quantified; average motion was 2.5 ± 1.4 min. Average total liver motion secondary to respiration in patients was 10.8 ± 2.5 mm. Instruments of varying lengths, including laparoscope, can be tracked to accuracies ranging from 1.4 to 2.1 mm within a 27-m3 (3 x 3 x 3-m) space. Conclusion: Interactive image-guided surgery appears to be feasible for open and laparoscopic hepatic procedures and may enhance future operative localization.