Abstract Background Laparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial. Methods/Design The Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed. Discussion After 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases. Trial registration The trial was registered in ClinicalTrals.gov ( NCT01516710 ) on 19 January 2012.