Background: The benefit of adjuvant chemotherapy in stage II colon cancer is unclear, and clear clinical or molecular marker are not available for decision making. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be prognostic in colorectal cancer and other tumours. Methods: For the CIRCULATE trial we enrol patients (pts) with colon cancer stage II in Germany (AIO), Austria (ABCSG) and Switzerland (SAKK). Microsatellite stable pts are screened after resection of the primary by analysing the tumour block with panel sequencing and measuring patient specific mutations in the postoperative plasma sample. MSI-H pts are excluded from the trial. ctDNA positive (ctDNApos) pts are randomised (2:1) to receive adjuvant capecitabine based chemotherapy or no chemotherapy. Oxaliplatin can be added according to investigator’s choice. ctDNA negative (ctDNAneg) pts are randomised (1:4) to be followed-up within the study or to receive standard follow-up outside the trial. Pts in the follow-up group and their investigators are blinded for the ctDNA result. The primary aim is to compare the disease free survival (DFS) in ctDNApos pts randomised to chemotherapy or to follow-up. Secondary aims are to compare the overall survival (OS) in ctDNApos pts with or without chemo, to compare the DFS and OS in ctDNApos vs. ctDNAneg follow-up pts, to describe the DFS and OS in ctDNAneg pts, to describe the location of recurrences/metastases according ctDNA status, the ctDNA clearance rate and time to ctDNA negativity during adjuvant chemotherapy, further translational endpoints, and safety. To demonstrate a treatment effect in the ctDNA group with a hazard ratio of 0.617 (3 year DFS rate of 42.5 % vs. 25 %), 231 ctDNApos will be randomised (approx. 2310 pts in total) from 2019 – 2022. Clinical trial information: NCT04089631