Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.