Background: A recently completed institutional phase II trial evaluated near-total neoadjuvant therapy (nTNT) for locally advanced rectal cancer using short course radiotherapy (SCRT) followed by four cycles of FOLFOX prior to total mesorectal excision (TME). A matched pair analysis is presented to compare clinical outcomes for nTNT with conventional chemoradiotherapy (CRT), TME, and postoperative chemotherapy (CT) for patients treated at our institution. Methods: 80 patients with cT3-4N0-2M0-1 rectal adenocarcinoma planned for resection of all tumor enrolled on a phase II study of preoperative SCRT (25 Gy to the involved mesorectum, 20 Gy to elective nodes, in 5 fractions) followed by four cycles of mFOLFOX6 before TME, with 6-8 cycles of adjuvant FOLFOX suggested. 69 patients with cM0 disease comprised the study cohort for this analysis. Patients treated with conventional CRT, followed by TME and adjuvant CT (63% ≥4 cycles adjuvant FOLFOX) were identified and matched 2:1 for exact cTNM stage. Kaplan-Meier with log-rank analysis was used to compare local control (LC), distant metastasis free survival (DMFS), disease free survival (DFS), and overall survival (OS), and two-tailed Mann-Whitney and Chi-squared tests used to compare cohort characteristics. Results: Median follow-up was 26 and 49 months for the study and control groups, respectively. Median age (57 vs. 55 years, p = 0.98) and distance from the anorectal ring (6 vs. 5 cm, p = 0.16) were similar for study and control groups, respectively. Pathologic complete response (pCR) and T-downstaging rates were 30% vs. 23% (p = 0.26) and 75% vs 50% (p = 0.001) in the study and match cohort, respectively. Actuarial 2-year LC (97% vs. 98%, p = 0.69) and OS (100% vs. 95% at 2 years, p = 0.57) were similar between the study and control groups, respectively. Two-year DMFS (94% vs. 80%, p = 0.016) and DFS (94% vs. 80%, p = 0.027) were significantly better in the study cohort. Conclusions: Controlling for institutional bias, exact cTNM stage, and tumor location, nTNT resulted in increased T-downstaging, superior DMFS and DFS, and similar LC and OS compared to conventional CRT.