Background: Short-course radiotherapy (SCRT) is an option in the neoadjuvant setting of resectable stage II-III rectal cancer, as well as in stage IV disease for local control without delay to initiate systemic treatment. Short-course radiotherapy is reported to be a comparable strategy for locally advanced rectal cancer. Limited data exist regarding the use of short-course radiation therapy when used as part of a non-surgical watch and wait approach. Methods: This is a retrospective analysis of all patients that underwent SCRT for rectal cancer at the Alexander Fleming Institute from 3/2014 to 6/2022. Results: 44 patients were treated with SCRT, 29 (66%) were male, with a median age of 59 years (46-73). Most of the patients had stage IV disease (26, 59,1%) followed by clinical stage II-III (18, 40,9%). 30 (68%) were localized in the middle with 14 (32%) in the lower rectum, by MRI imaging. In locally advanced disease 5/18 had T4 disease and 7/18 had N≥2. 14/18 patients (89%) underwent SCRT followed by consolidation chemotherapy (ChT) and 4 (11%) had induction ChT followed by SCRT. In metastatic disease 14/26 patients (53.84%) underwent SCRT followed by consolidation ChT, 10 (38.46%) had induction ChT followed by SCRT, and 2 (7.7%) received only SCRT. 29 (65.9%) of patients underwent surgery. 17/29(58.6%) had metastatic disease and 12/29 (41.4%) had locally advanced disease. Pathological response rates in operated patients were 2 (6.9%). 8 (18.2%) cases had a clinical complete response (cCR) (n=6 stage II-III and n=2 stage IV). Five (27.7% of the locally advanced group) patients with cCR underwent watch and wait with 1 local recurrence after 14 months. The remainder is disease free with a median follow-up time of 20 months (IC 95%: 15.14-24.85). Those that underwent SCRT following chemotherapy were more likely to have AEs compared to those that had chemotherapy following SCRT (11/30, 36.7% vs 25%, p=0.02). Conclusions: Our work shows that in a subgroup of patients diagnosed with LARC treated with SCRT followed by Chemotherapy, surgical treatment could be deferred after achieving a complete clinical response. The shorter time involved by SCRT allowed for less treatments with similar toxicity to long-course treatment regimens. SCRT is a reasonable option for local disease control in stage IV disease.