Background: ACHIEVE, as part of the IDEA collaboration, was a multicenter trial randomizing patients with stage 3 resected colon cancer to either 3 versus 6 months of adjuvant FOLFOX/CAPOX. We previously reported that the hazard ratios (HRs) in disease-free survival (DFS) of 3 versus 6 months duration according to risk stage (low-risk [T1-3 and N1] or high-risk [T4 or N2]) and regimen (FOLFOX or CAPOX) as well as in overall population were consistent with those observed in the whole IDEA. This study aimed to clarify the significance of post-operative serum carcinoembryonic antigen (CEA) on DFS in stage 3 colon cancer. Methods: Eligibility included post-operative serum CEA value of ≤10 ng/ml at registration in the ACHIEVE trial, which enrolled 1313 patients between 2012 and 2014, out of whom 1291 pts were the modified ITT (mITT) population and used in this study. The cutoff values of CEA analyzed for prognostic analyses were the median value (1.8 ng/ml) in the mITT, the upper limit of normal (ULN) level (5.0 ng/ml), and the half of ULN (2.5 ng/ml). The association of post-operative CEA with DFS were measured by Cox regression analyses. Results: Of the 3 cutoff values, the ULN (5.0 ng/ml) was associated with DFS more strongly than the median (1.8 ng/ml) or half of ULN (2.5 ng/ml), with a HR of 1.75 (95%CI, 1.24-2.46) (Table). The 99 patients (7.7%) were identified as the CEA > ULN and 1192 (92.3%) as < ULN. In univariate analysis, regimen (CAPOX or FOLFOX), ECOG PS (0 or 1), T factor (T1-3 or T4), N factor (N1 or N2-3) and CEA ( < ULN or > ULN) were significantly associated with DFS. Multivariate Cox regression identified CEA > ULN as an independent poor risk factor (HR = 1.45; 95%CI, 1.03-2.05). Shorter DFS in patients with CEA > ULN than in those with CEA < ULN was consistently observed in each subgroup of baseline factors, including treatment duration, regimen, age, gender, PS, T-stage, N-stage, no of lymph nodes examined, and tumor location; no interaction was observed between CEA and these factors. Conclusions: Post-operative serum CEA is also a strong prognostic factor for DFS in stage 3 colon cancer. Clinical trial information: 000008543.