Background <p>Patients with clinical Stage II or III rectal cancer routinely receive neoadjuvant radiotherapy and chemotherapy. But pelvic magnetic resonance imaging may identify patients who can safely avoid neoadjuvant treatments. We evaluated 2-year oncologic outcomes for patients with “margin-clear” Stage II or III rectal cancer going directly to a planned low anterior resection.</p> Patients and Methods <p>This prospective, non-randomized, phase II trial was performed at 12 high-volume hospitals across Canada. Patients proceeded directly to a planned low anterior resection if they met the staging magnetic resonance imaging (MRI) criteria for “good prognosis” rectal cancer, including distance &gt; 1 mm between primary tumor, tumor nodule, or positive mesorectal lymph node and the mesorectal fascia. Primary outcomes were 2-year rates of local recurrence, disease free survival, and overall survival.</p> Results <p>From 30 September 2014 to 31 December 2019, 139 patients met the inclusion criteria and were recruited for the study. Final pathology was Stage 1 in 59 (42%) patients and Stage II/III in 80 (58%). For the 80 Stage II or III patients, 2-year rates for local recurrence, disease free and overall survival were 1% (95% confidence interval [CI] 0–6.8), 85% (95% CI 75.3–92.0), and 99% (95% CI 93.2–100), respectively. Only 8% (6/80) (95% CI 2.8–15.6) received adjuvant radiotherapy. Preoperative staging MRI findings over-staged 30 of 59 pathology-confirmed Stage I patients (51%) (95% CI 37.5–64.1) to a clinical Stage II or III status.</p> Conclusions <p>Among patients planned for a low anterior resection and with MRI criteria predicting margin-clear Stage II or III rectal cancer, a direct-to-surgery approach was associated with excellent 2-year oncologic outcomes and low use of radiation.</p> <p><i>Trial Registration</i>: ISRCTN.com Identifier: ISRCTN05107772</p>