Background: Quality and practice guidelines from the American College of Surgeons Commission on Cancer (CoC) and the National Comprehensive Cancer Network (NCCN) recommend neoadjuvant chemoradiation (NCR) for locally advanced rectal cancer (LARC). We examined guideline adherence in a healthcare system serving a region with significant socioeconomic disparities and poor cancer outcomes. Methods: We performed a retrospective analysis of patients from 2005-2014 with stage II and III rectal cancer in our local 5- hospital healthcare system in the Mid-South region of the US. We examined the associations between guideline adherence and patient demographic, socioeconomic, and clinicopathologic data. Results: Of 157 stage II/III RC patients, 96 (61.1%) received NCR. By univariate analysis, factors associated with receipt of NCR included white race versus non-white (OR = 2.14, p = 0.024), private insurance versus no or public insurance (OR = 2.70, p = 0.005), employed status versus unemployed (OR = 2.29, p = 0.031), age at diagnosis (OR = 0.74, p = 0.032), and appropriate local staging with EUS or MRI (OR = 6.67, p = < 0.0001). Those who were diagnosed and treated later in the study period were more likely to get NCR (OR per 1 year = 1.20, p = 0.006). In addition, receipt of NCR was protective against death at time of follow up (OR = 0.41, p = 0.009). By multivariate analysis, those with private insurance (OR = 2.51, p = 0.023), younger age at diagnosis (OR per 10 years = 1.39, p = 0.048) and with appropriate local staging (OR = 6.67, p < 0.0001) were more likely to have received NCR. Conclusions: Guideline adherence for LARC in our system, which serves a population with socioeconomic disparities, is relatively low. Sociodemographic factors such as employment and race influenced receipt of NCR, while insurance status and age were independent determinants. Despite some increase in compliance over time, adherence to NCR for LARC remains lower than expected and represents an important target for improvement efforts.