Objective <p>This study aimed to investigate the impact of anastomotic orientation (Upward vs. Downward) in Roux-en-Y reconstruction on duodenal stump leakage(DSL) incidence following radical total gastrectomy for gastric cancer. Additionally, this study explored the safety, feasibility, and related risks associated with standard upward-oriented Roux-en-Y anastomosis in radical total gastrectomy.</p> Methods <p>This retrospective study involved 144 patients who underwent laparoscopic or open radical total gastrectomy by the same surgical team at a single centre. Patients were categorized into two distinct groups according to the type of Roux-en-Y anastomosis: the upward-oriented anastomosis group (<i>n</i> = 60) and the downward-oriented anastomosis group (<i>n</i> = 84). In the upward-oriented group, after completing the dissection of the gastric tumour and regional lymphadenectomy, the specimen was retrieved, and a gastrojejunostomy was performed. The proximal and distal ends of the small intestine were subsequently anastomosed via either a side-to-side or an end-to-side technique.</p> Results <p>No statistically significant differences were observed in the general clinical data between the groups that underwent upward-oriented and downward-oriented Roux-en-Y anastomosis (all <i>P</i> &gt; 0.05), making the groups comparable. The incidence of DSL was greater in the downward-oriented anastomosis group than in the upward-oriented anastomosis group; however, this difference was not statistically significant [2.4% (2/84) vs. 0, <i>p</i> = 0.23]. The reoperation rate due to DSL was also higher in the downward-oriented group [1 (1.2%) vs. 0, <i>p</i> = 0.40], and one patient in the downward-oriented group died due to DSL [1 (1.2%) vs. 0, <i>p</i> = 0.40]. The duration of postoperative abdominal drainage was shorter in the upward-oriented group than in the downward-oriented group [90% (54/60) within less than 6&#xa0;days vs. 57.1% (48/84), <i>p</i> &lt; 0.001]. No statistically significant differences were observed between the two groups with respect to operation time, intraoperative blood loss, number of lymph nodes dissected, TNM stage, length of postoperative hospital stay, or postoperative complications unrelated to DSL.</p> Conclusion <p>DSL is a rare yet serious complication. The application of upward-oriented Roux-en-Y anastomosis for digestive tract reconstruction after total gastrectomy for gastric cancer demonstrates comparable efficacy in the recovery of postoperative digestive function to downward-oriented anastomosis methods. Additionally, the upward-oriented approach does not increase the incidence of postoperative DSL or the reoperation rate, nor does it increase the incidence of other catheter-related complications, offering a safe and viable alternative approach. This study provides clinical evidence to support the standardization of Roux-en-Y reconstruction techniques. In addition, conducting early postoperative abdominal CT examinations and providing timely symptomatic treatment can help reduce the severity of duodenal stump leakage and decrease the likelihood of reoperation.</p>