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Aim of this study was to assess the feasibility and safety of a 1064 nm Nd:YAG laser for left lateral liver resection in a porcine model. Laparoscopy and hand-assisted laparoscopic surgery were evaluated and compared with conventional open surgery.Animals were randomized for open, hand assisted, and laparoscopic left lateral liver lobe resection. Primary endpoints were intraoperative blood loss, dissection time, laboratory changes, and abdominal wall adhesions. In addition intraoperative cardiopulmonary data, postoperative clinical parameters, and necropsy findings were analyzed.Liver resection was successful in all animals without intraoperative or postoperative mortality. Laparoscopic dissection time was significantly increased. Average blood loss was 340 mL for open surgery and 320 mL for hand-assisted surgery. Blood loss during laparoscopy was significantly smaller with a mean of 180 mL. Postmortem findings revealed extensive adhesions for open surgery whereas hand assisted and laparoscopic animals showed limited adhesions in the upper abdomen.Nd:YAG laser-based liver resection is a potentially safe and feasible technique. The minimal access approaches show comparable results to the open technique with reduced abdominal trauma and less adhesions. Laparoscopy was more time consuming but showed reduced blood loss compared with both other groups.