Background: in 2021 ASCO has updated guidelines on adjuvant therapy for stage II colon cancer with the statement: “Patients with T4 tumors are at higher risk of recurrence and should be offered adjuvant chemotherapy, whereas patients with other high-risk factors, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, or grade BD3 tumor budding, may be offered ACT”. We performed a single-center retrospective study to assess the prognostic role of postoperative tumor stage T4 and T3 with ≥2 negative prognostic factors in patients with resected stage II colon cancer. Methods: We retrospectively analyzed 1457 pts with stage I-III colon cancer treated in Russian Cancer Research Center n.a. N.N. Blokhin from 2001 to 2015. We included pts with resected stage II colon cancer with following negative prognostic factors: T4; sampling of fewer than 12 lymph nodes in the surgical specimen; perineural or lymphatic invasion; poorly or undifferentiated tumor grade; intestinal obstruction; and tumor perforation. Three cohorts were studied: pts with pT4N0M0 with no other high-risk factors (group A), pts with pT4N0M0 with additional high-risk factors (group B), and pts with pT3N0M0 with ≥2 high-risk factors (group C). The primary study endpoint was 3-year disease-free survival (DFS). The secondary endpoint was 5-year overall survival (OS). Statistical analysis was done with SPSS v.20. Results: 164 pts met the inclusion criteria with 17 (10%) pts in group A, 90 (55%) pts in group B, and 57 (35%) pts in group C. Adjuvant chemotherapy was performed in 8 (47%), 25 (28%), and 9 (16%) pts, respectively (p = 0.035). At a median follow-up of 62 months (range, 2-135 months), the 3-year DFS was 82%, 68%, and 78% for groups A, B, and C, respectively (HR, 1.55; 95% CI, 0.99-2.4; p = 0.053). No difference in 3-year DFS was found between group A and C (HR, 1.0; 95% CI, 0.34-3.2; p = 0.9). The 5-year OS was 75%, 65%, and 78% for groups A, B, and C, respectively (HR, 1.38; 95% CI, 0.84-2.3; p = 0.2). Conclusions: Patients with pT4 with additional high-risk features had worse overall survival compared to other subgroups with resected stage II colon cancer. There was no difference in survival rates between patients with pT4 with no additional negative prognostic factors and pT3 with ≥2 negative prognostic factors. Therefore, we propose that patients with pT4 as well as with pT3 with ≥2 negative prognostic factors are at a higher risk of recurrence and should be offered adjuvant chemotherapy.