Background and Aim: Although acute upper gastrointestinal bleeding (UGIB) can lead to anemia, evidence regarding the effects of oral iron supplementation on UGIB-induced anemia following discharge remains lacking. The present study aimed to investigate the effects of oral iron supplementation on hemoglobin response and iron storage in patients with anemia secondary to nonvariceal UGIB. Methods: This randomized controlled trial included 151 patients with nonvariceal UGIB who had anemia at discharge. Patients were assigned to a 1:1 block in which they were either administered 6 weeks of 600 mg/d oral ferrous fumarate (treatment group, n = 77) or treated without iron supplementation (control group, n = 74). The primary outcome was composite hemoglobin response (hemoglobin elevation greater than 2 g/dL or no anemia at the end of treatment [EOT]). Results: The proportion of patients achieving composite hemoglobin response was greater in the treatment group than in the control group (72.7% vs 45.9%; adjusted risk ratio [RR], 2.980; P = 0.004). At EOT, the percentage change in the hemoglobin level (34.2 ± 24.8% vs 19.4 ± 19.9%; adjusted coefficient, 11.543; P < 0.001) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 μg/L and a transferrin saturation <16% were lower in the treatment group (all P < 0.05). No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups. Conclusion: Oral iron supplementation exerts beneficial effects on anemia and iron storage following nonvariceal UGIB without significantly impacting rates of adverse effects or adherence.interpreted the data. Keerati Akarapatima: Designed and conceptualized the study and acquired and analyzed the data. Komsai Suwanno: Dsesigned and conceptualized the study and interpreted the data. Attapon Rattanasupar: Acquired, analyzed, and interpreted the data and drafted the manuscript. Bancha Ovartlarnporn: Analyzed and interpreted the data and drafted the manuscript. Varayu Prachayakul: Designed and conceptualized the study and revised the manuscript for important intellectual content. Ethics approval: This single-center, open-label, randomized controlled trial was conducted in the Department of Internal Medicine at Hatyai Hospital between March 2019 and February 2021. The study was approved by the Institutional Review Board (protocol number 36/2561) and performed in accordance with the Declaration of Helsinki. Patient consent: All enrolled patients provided written informed consent. Clinical trial registration: The study was registered with the Thai Clinical Trials Registry (TCTR20190225002) prior to enrollment of the first participant. All authors have read and approved the final version of the manuscript.