Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA.