INTRODUCTION Transversus abdominis plane (TAP) blocks are used for post-operative pain management, but their efficacy remains unclear. We aim to investigate the effect of two TAP block methods in minimally invasive colon surgery. METHODS This will be a double-blind, randomised and controlled multicentre trial including 360 adults who are planned for elective minimally invasive colon surgery with curative intent for colon neoplasia. The participants are randomised to one of three arms: active ultrasound-guided TAP (US-TAP) and placebo laparoscopic assisted TAP (L-TAP), placebo US-TAP and active L-TAP, or placebo US-TAP and placebo L-TAP. The primary outcome is morphine dose equivalents administered during the first 24 hours after surgery. Secondary outcomes are pain on the first post-operative day, length of stay, post-operative nausea and vomiting, and quality of recovery measured using the Quality of Recovery 15 questionnaire. Statistical analysis will determine any superiority of US-TAP and L-TAP versus placebo, and any non-inferiority of L-TAP compared with US-TAP. The latter will only be tested if superiority to placebo is shown. Primary and secondary outcomes will be analysed as intention-to-treat regarding superiority and as intention-to-treat and per protocol regarding non-inferiority. CONCLUSION This will be the first ever blinded multicentre trial comparing L-TAP, US-TAP and placebo in daily clinical practice. The study has the potential to determine the role of the TAP in minimally invasive colon surgery. FUNDING A & JC Tvergaards Fond, Helen Rudes Fond, Fru Olga Bryde Nielsens Fond, Aage og Johanne Louis-Hansen Fond, Medicine & Treatment Research Fund of the Danish Regions and a Research Grant from Copenhagen University Hospital – North Zealand Hospital. TRIAL REGISTRATION ClinicalTrials.gov: NCT04311099.