Background: In multiple studies, preoperative long-course radiotherapy (PLRT) in conjunction with concurrent chemotherapy (PLCRT) and preoperative short-course radiotherapy (PSRT) with immediate surgery have demonstrated comparable outcomes regarding late morbidity, local control, and prolonged survival. However, long-course RT demonstrated a more favorable pathological complete response (PCR). The acute radiation toxicities associated with the short-course program are considerably lower than those observed in standard CRT. Significant benefits are associated with postponing surgery after neoadjuvant therapy for rectal cancer. As a result, a strategy of short-course RT and then consolidation chemotherapy prior to surgical resection is developed to achieve these benefits. Objective: This study aimed to evaluate the treatment outcome, safety, and feasibility of preoperative short-course hypo fractionated RT (SCRT) followed by chemotherapy versus standard conventional long-course concurrent chemoradiotherapy (LCRT) for locally advanced rectal cancer (LARC) patients. Patients and methods: This phase II prospective trial included 59 patients through the period from May 2020 to February 2021 in Sohag Cancer Center and Sohag University Hospital with a median follow-up of 31 months (range 4:37). Thirty cases were assigned to the experimental group (SCRT) and twenty-nine were assigned to the standard group (LCRT). The study was performed on locally advanced rectal cancer (LARC) cases and were randomized to neoadjuvant short-course RT followed by chemotherapy or preoperative conventional long-course CRT. Pathological response and treatment-related toxicity constituted the main endpoints. EFS, LFFS, DRFS, and OS were thesecondary endpoints. Results: No significant variations were reported between the SCRT and LCRT groups as regards death rate and locoregional failure rate, or distant recurrence. In subgroup analysis for cases who were subjected to resection, no significant variations were reported between the SCRT and LCRT groups regarding postoperative (pathological) stages, pathological complete response rates, and grades of tumors. No significant variation was reported between the two groups as regards most of treatment-related toxicities, but the SCRT group had significantly lower radiation therapy-induced toxicities than the LCRT group. Conclusion: Patients diagnosed with LARC may benefit from SCRT followed by chemotherapy as a substitute for conventional CRT. SCRT with delayed surgery showed comparable efficacy to conventional LCRT.