INTRODUCTION: Gastrointestinal (GI) bleeding is a significant clinical presentation in elderly patients, where comorbidities, polypharmacy, and drug-drug interactions markedly increase the risk of bleeding. The aim of this study was to evaluate the types of medications prescribed during the six months prior to the patients' admission and the potential risks associated with drug interactions in patients aged 65 and older diagnosed with GI bleeding. METHODS: This retrospective study included 49 patients aged 65 and older who were admitted to the emergency department of Kırklareli Training and Research Hospital with a diagnosis of GI bleeding between January 1 and December 31, 2022. Patient demographics, type of GI bleeding (upper or lower), duration of hospital stay, clinical outcomes, and medications prescribed during the six months prior to hospitalization were recorded. Statistical analyses were performed using GraphPad Prism 8.0. Continuous variables were reported as mean±standard deviation and categorical variables were analyzed using Fisher's exact test and Chi-square test, with a significance level of p<
0.05. RESULTS: The study included 49 patients, comprising 25 (51.02%) males and 24 (49.98%) females, with a mean age of 78.4±7.6 years. Female patients had a significantly higher mean age than males (p=0.045). Upper GI bleeding (81.6%) was more prevalent than lower GI bleeding (18.4%), with no statistically significant gender difference (p=0.7252). The mortality rate was 10.2%, with all deceased patients being female and diagnosed with upper GI bleeding (p=0.0226). A total of 110 medications were prescribed during the six months prior to hospitalization. Drug interactions were identified in 28 patients, with 67.9% classified as moderate and 28.6% as major. NSAIDs, anticoagulants, and antidepressants were the most frequently involved drug groups, significantly heightening the risk of GI bleeding. CONCLUSION: Polypharmacy and drug-drug interactions are critical factors that contribute to the increased risk of GI bleeding in elderly patients. Comprehensive evaluation of medication regimens and strategies to mitigate polypharmacy are essential for improving patient safety and outcomes in this population.