Background: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer (LARC). Using this approach, maChT administration is delayed several months, leading to concern for high rates of distant failure. To reduce the rate of systemic failure, a novel treatment approach known as total neoadjuvant therapy (TNT) has been increasingly employed, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database (NCDB) to examine temporal trends in TNT usage, as well, as any potential effect on survival. Methods: We queried the NCDB for patients diagnosed with LARC (Stage II-III) from 2004–2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 days prior to the start of nCRT. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival, with log-rank statistics used to assess statistical significance between groups. Multivariable cox regression was used to identify predictors of survival and propensity score analysis was used to account for indication bias. Results: We identified 9,066 eligible patients, with 8,812 and 254 patients receiving nCRT and TNT, respectively. Nodal involvement and Stage III disease were predictive of TNT use, as well as, treatment in in more recent year. TNT and nCRT had similar 5-year survival, 76% and 78%, respectively. MVA identified age > 58, increased income, urban location, academic treatment facility, and lower co-morbidity score as predictors of worse OS. Multivariable analysis with propensity score demonstrated increased age, higher comorbidity score, higher grade, African American race, and gender as predictive of worse OS. Conclusions: Our data demonstrates a trend toward increasing TNT use, particularly in patients with greater nodal involvement or clinical stage. Despite worse disease characteristics, patients treated with TNT had similar survival to those receiving standard nCRT. Randomized trials are underway to further define the clinical benefit of TNT.