Abstract Total neoadjuvant therapy (TNT) is a treatment strategy for rectal cancer that includes a course of chemotherapy and a separate course of chemoradiation before definitive surgery. The use of TNT has increased in recent years and carries the potential for improved sphincter preservation and a significant risk reduction of locoregional recurrence. One criterion of the National Accreditation Program for Rectal Cancer is to begin definitive treatment within 60 days of a patient’s diagnosis of rectal cancer. The objective of this study was to evaluate the association of social determinants of health and healthcare-related factors with starting TNT 60 days or more after diagnosis using data from the National Cancer Database (NCDB). Patients aged 18 years and older diagnosed with primary rectal cancer between 2016 and 2019, who underwent NCCN recommended TNT regimen followed by definitive surgery at a Commission on Cancer (CoC)-accredited facility and did not die before receiving surgery were eligible for the current study. We included 3,210 patients in the analytic sample who did not have the following conditions: clinical stage IV, clinical stage T1N0 or lower, non-adenocarcinoma histology, and adjuvant therapy use. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for factors potentially associated with starting TNT more than 60 days after a cancer diagnosis. The median age of patients included in the study was 57 years old, with a majority of them starting TNT within 60 days (87.5%), were males (62.3%), and reported as Non-Hispanic White race and ethnicity (76.7%). Furthermore, 35.0% had a median household income of $63,333 or more, 57.7% had private insurance/managed care, 65.0% traveled within 30 miles to their treatment facility, and 49.1% lived in a zip code where less than 10.9% of adults age 25 or older did not graduate from high school. In multivariable models, factors positively associated with starting TNT after 60 days or more were uninsured status (OR 2.93, CI: 1.84, 4.67), living in a zip code with more than 10.8% of adults age 25 or older not graduating from high school (OR 1.66, CI: 1.22, 2.25), traveling more than 30 miles to the treatment facility (OR 1.63, CI: 1.20, 2.20), treatment with an academic/research program (OR 1.51, CI: 1.13, 2.02), Medicaid as primary insurance (OR 1.50, CI: 1.03, 2.19), Hispanic ethnicity (OR 1.44, CI: 1.00, 2.07), male (OR 1.28, CI: 1.00, 1.65) and age (1.02, CI: 1.01, 1.04). In conclusion, results from this study show that social determinants of health and other healthcare-related factors are significantly associated with those who started TNT more than 60 days after a rectal cancer diagnosis. Further investigation is ongoing to understand the impact of delays in TNT and other treatment regimens for rectal cancer. Citation Format: Megan T. Mai, Zheng Shi, Duke Appiah. Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P021.