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Purpose/objectives Induction chemotherapy followed by chemoradiation and surgical resection in rectal cancer, known as total neoadjuvant therapy (TNT), is associated with improved pathologic complete response (pCR) rates. The National Cancer Database was utilized to identify factors associated with pCR and survival following treatment with TNT compared to standard neoadjuvant chemoradiation (nCRT). Materials/methods The National Cancer Database was queried from 2004 to 2015 for patients with locally advanced, non-metastatic rectal cancer. We identified 16,299 patients receiving neoadjuvant chemotherapy and radiation followed by definitive surgical resection. Patients were stratified by treatment received, either TNT (n=350) or nCRT (n=15,949). Multivariate binomial regression analysis and propensity matching were used to evaluate predictors of pCR. Kaplan-Meier and Cox multivariate analysis of survival were performed. Results Median follow-up was 38 months vs 53 months in the TNT vs nCRT groups, respectively. There were more patients with T4 or node-positive disease in the TNT group. There was a trend towards improved pCR in the TNT group (p=0.053). Patients achieving pCR had improved 5-year overall survival (OS) of 85.1%. The 5-year OS was not improved for TNT (76.2%) over nCRT (69.9%) (p=0.19). Pelvic nodal pCR was significantly higher in the TNT group (72%). When stratified by clinical stage, patients with cT3 (p=0.038) or cN1 (p=0.049) disease had improved OS with TNT. Conclusions Compared to nCRT, TNT is correlated with higher rates of complete pelvic nodal clearance in patients with locally advanced rectal adenocarcinoma. The use of TNT showed improved survival in patients with cT3 and cN1 disease, indicating a potential benefit for patients with less advanced disease.