Purpose: The outcomes of open colorectal anastomosis of side-to-end vs. end-to-end in non-emergent sigmoid and rectal cancer surgery in adults were compared. Methods: A randomized controlled trial on individuals with sigmoid and rectal cancers was conducted between September 2016 and September 2018. Results: The mean age was 62.58 ± 12.3 years in the side-to-end anastomotic (SEA) group and 61.03 ± 13.98 years in the end- to-end anastomotic (EEA) group. Except for the operative time, intraoperative data revealed no significant differences be- tween the studied groups, and the SEA group revealed that the mean anastomotic time was significantly shorter. Periopera- tive blood loss, length of stay, reoperation, inpatient death, infection, and bleeding were significantly associated with leakage. There is a statistically significant change regarding the range of bowel frequency in the EEA group only (P = 0.04). There is a statistically significant difference regarding incontinence for flatus in the SEA group only (P ≤ 0.001). A statistically signifi- cant change in both groups regards incontinence for liquid stools (P ≤ 0.001) and clustering of stools (P ≤ 0.001 and P = 0.043). The quality of life in the SEA group significantly dropped at 6 months and then returned to baseline as regards to physical well-being (PWB), functional well-being (FWB), and colorectal cancer symptoms (CCS) with no difference as regards SWB and EWB, while in the EEA group, the exact change happened only as regard PWB and FWB, but SWB and CCS percentage did not return to baseline. Conclusion: The SEA group offers a safe alternative approach to the EEA group. Keywords: Colorectal anastomosis; Leakage; Quality of life; Rectal neoplasms; Stapler