BACKGROUND : Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective analysis to determine whether adjuvant chemotherapy imparts survival benefit among this population. METHODS : The National Cancer Database (NCDB) was queried to identify LARC patients with pCR following neoadjuvant chemoradiation. The cohort was stratified by receipt of adjuvant chemotherapy. Multiple imputation and a Cox proportional hazards model were employed to estimate the effect of adjuvant chemotherapy on overall survival. RESULTS : There were 24,418 patients identified in the NCDB with clinically staged II or III rectal cancer who received neoadjuvant chemoradiation. Of these, 5606 (23.0%) had pCR. Among patients with pCR, 1401 (25%) received adjuvant chemotherapy and 4205 (75%) did not. Patients who received adjuvant chemotherapy were slightly younger, more likely to have private insurance, and more likely to have clinically staged III disease, but did not differ significantly in comparison to patients who did not receive adjuvant chemotherapy with respect to race, sex, facility type, Charlson comorbidity score, histologic tumor grade, procedure type, length of stay, or rate of 30-day readmission following surgery. On adjusted analysis, receipt of adjuvant chemotherapy was associated with a lower risk of death at a given time compared to patients who did not receive adjuvant chemotherapy (HR 0.808; 95% CI 0.679-0.961; p = 0.016). CONCLUSIONS : Supporting existing NCCN guidelines, the findings from this study suggest that adjuvant chemotherapy improves survival for LARC with pCR following neoadjuvant chemoradiation.