Background: The most common therapy for locally advanced (T3/4 or N+) rectal cancer (LARC) consists of preoperative chemoradiotherapy (chemoRT) followed by surgery and adjuvant chemotherapy. Recently, use of total neoadjuvant therapy (TNT) with preoperative chemotherapy in addition to chemoRT prior to resection has been accepted as an alternative. Methods: Of 811 consecutive patients (pts) who presented with LARC at our cancer center in 2009-2015, 320 received chemoRT with planned adjuvant chemotherapy, and 308 received TNT (induction FOLFOX/CAPOX chemotherapy followed by chemoRT). Treatment and outcome data for those two cohorts were compared. Results: Pts in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort (p < 0·005 and p < 0·001, respectively). The complete response (CR) rate, which includes pathological CR (pCR) and clinical CR (cCR) at 6 months post-treatment, was 21% in the chemoRT with planned adjuvant chemotherapy cohort and 36% in the TNT cohort. The median follow-up was 40 months in the chemoRT with planned adjuvant chemotherapy cohort and 23 months in the TNT cohort. Fewer distant recurrences were seen in patients who had T downstaging (p < 0·001), N downstaging (p < 0·005), a cCR (p = 0·005), or a pCR (p < 0·005). There was no statistically significant difference in distant-recurrence-free survival between the two cohorts. Conclusions: Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines for rectal cancer treatment, which categorizes TNT as a viable treatment strategy that facilitates superior compliance and delivery of systemic therapy. Given its high CR rate, TNT may be beneficial as part of a nonoperative treatment strategy aimed at organ preservation.