Objective Tranexamic acid (TXA) is an antifibrinolytic agent used to control bleeding in different circumstances. We conducted a randomized controlled trial to assess the efficacy and safety of locally administered TXA in upper gastrointestinal hemorrhage. Methods This single-center, double-blind, randomized controlled trial was performed in a tertiary emergency department (ED) in patients presenting with upper gastrointestinal bleeding symptoms between 2016 and 2018. The patients received either 2000 mg of 5% TXA in 100 mL of isotonic saline solution or 100 mL isotonic saline (control group) via the nasogastric route. As a composite outcome, recurrent endoscopy need, rebleeding, surgery need, recurrent admission to the ED, and mortality parameters were evaluated at the end of a one-month period. Results During the study period, 78 patients were randomized into the TXA group, and 79 patients were randomized into the isotonic saline group. The majority of the bleedings (61%) were in Forrest class 3, and the most frequent cause was peptic ulcer disease. The composite outcome occurred in 25 of the TXA patients (32.1%) and 23 of the isotonic saline patients (29.1%); no statistically significant difference was found between the groups (P = 0.690). In addition, no statistically significant differences were observed between the TXA and control groups regarding mortality (10.3 vs 12.7%;P = 0.637), recurrent ED admission (17.9 vs 12.7%;P = 0.357), or thromboembolic complications (3.8 vs 1.3%;P = 0.367). Conclusion Locally administered TXA confers no additional benefit over standard care in patients with upper gastrointestinal hemorrhage.