INTRODUCTIONThe predictive utility of high-risk features (HRFs) and microsatellite instability (MSI) status for adjuvant chemotherapy (ACT) in patients with stage II colon cancer remains unclear. We examined the impact of HRFs and MSI in predicting the benefits of adjuvant ACT in patients with stage II colon cancer.MATERIALS AND METHODSWe included 1801 patients with resected stage II colon cancer who underwent ACT (5-fluorouracil [FU] and oxaliplatin) or surgery alone between January 2010 and December 2017. The primary outcomes were overall survival (OS) and disease-free survival (DFS).RESULTSAmong MSI-high patients with HRFs, patients who received 5- FU and oxaliplatin-based ACT had significantly higher OS and DFS than patients who did not, with no significant difference between those who received 5-FU and oxaliplatin as ACT. Among MSI-low/microsatellite stable patients with HRFs, patients who received 5-FU and oxaliplatin as ACT had significantly higher OS and DFS than patients who did not, with no significant differences between those who received 5-FU and oxaliplatin as ACT. Among patients who did not receive ACT, OS and DFS were 95.0 % and 91.2 % for patients without HRFs, respectively, and 84.4 % and 75.0 % for patients with HRFs, respectively. ACT improved the survival rates of patients with HRFs (OS: 84.4 %→95.9 %, DFS: 75.0 %→88.9 %).CONCLUSIONSACT can be recommended for patients having stage II colon cancer with one or more HRF(s) for recurrence, regardless of the MSI status. In patients with HRFs, we observed no significant difference regarding survival between those who received 5-FU and oxaliplatin-based ACT.