Objective: To investigate the impact of early postoperative chemotherapy on the clinical outcomes in patients with stage III colorectal cancer. Methods: The clinical data of 218 patients with stage III colorectal cancer treated from January 2010 to February 2014 were retrospectively analyzed. According to the time of initiation of chemotherapy, patients were divided into early chemotherapy group (started chemotherapy ≤3 weeks after surgery in 118 cases) or late chemotherapy group (started chemotherapy >3 weeks and ≤8 weeks after surgery in 100 cases). The variables that included progression-free survival, and 2-year survival and recurrence rate, as well as incidence of postchemotherapy adverse reactions and health-related quality of life score between the two groups were analyzed. Results: There was no difference in baseline data between the two groups (all P>0.05). In early chemotherapy group compared with late chemotherapy group, the progression-free survival time was significantly prolonged (876.4 d vs. 765.4 d, P=0.007), 2-year survival rate was somewhat elevated, but the difference reached no statistical significance (89.0% vs. 80.0%, P=0.091), 2-year recurrence rate was significantly reduced (17.0% vs. 34.0%, P=0.004), incidence of each postchemotherapy adverse reaction showed no statistical difference (all P>0.05), and the score for health-related quality of life at 12 months after surgery was significantly increased (71.9 vs. 64.1, P<0.001). Conclusion: For patients with stage III colorectal cancer, early postoperative chemotherapy can effectively prolong the progression-free survival, decrease recurrence and improve the health-related quality of life.