The controversy surrounding the continuation of postoperative adjuvant chemotherapy (AC) for locally advanced rectal cancer patients who underwent neoadjuvant therapy (NAT) still existed. The study aimed to identify the individuals that would benefit from AC from those with stage ypII/III rectal cancer. Data for this retrospective study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and the local database. Subgroup differentiation of the beneficiary population by classification and regression tree analysis. The primary endpoint was overall survival (OS). 15,671 patients were included from the SEER database and 508 patients from local database. The proportions receiving AC were 41.9% in the SEER database and 77.6% in local database, respectively. Analysis results illustrated that the AC benefited population in the SEER database was characterized as: stage ypT4/N + patients (HR 0.75, 95% CI 0.69-0.82, p < 0.001); stage ypT3N0 patients aged 70 years or older (HR 0.69, 95% CI 0.56-0.83, p < 0.001). Moreover, stage ypT4/N + patients also significantly benefited from AC in local database (HR 0.48, 95% CI 0.31-0.74, p < 0.001). The analysis of the two databases showed that stage ypT3N0 patients aged < 70 years could not significantly benefit from AC (HR 0.90, p = 0.114 in the SEER database; HR 0.90, p = 0.960 in local database). Postoperative adjuvant chemotherapy provides a significant benefit in patients with stage ypT4/N + rectal cancer following neoadjuvant therapy. Our study discovered that locally advanced rectal cancer patients with aggressive tumors might benefit from postoperative adjuvant chemotherapy and prolonged the survival.