Background Peptic ulcer disease continues to pose a significant clinical challenge, especially in patients at risk for complications such as gastrointestinal bleeding and recurrence. Both endoscopic and pharmacological treatments are commonly employed, yet their comparative effectiveness in routine care remains underexplored. Objective This study aimed to compare clinical outcomes between endoscopic and pharmacological treatment approaches in patients with gastric or duodenal ulcers. Methods A prospective cohort study was conducted at two tertiary care hospitals from January to June 2024. A total of 120 patients were enrolled, with 60 receiving endoscopic therapy and 60 managed pharmacologically. Demographic, clinical, and endoscopic data were collected. Key outcomes included ulcer healing at 4 weeks, rebleeding within 3 months, ulcer recurrence, hospital stay duration, need for surgery, and treatment-related adverse events. Data were analyzed using SPSS version 26. Appropriate statistical tests were applied based on data type and distribution, including logistic regression for adjusted outcome analysis. Results Ulcer healing at 4 weeks was significantly higher in the endoscopic group (93.3% vs. 65.0%, p < 0.001). Rebleeding and ulcer recurrence were significantly lower in the endoscopic group. Patients receiving endoscopic therapy also had shorter hospital stays and required fewer surgical interventions. Logistic regression confirmed the treatment group as an independent predictor of healing and recurrence. Conclusion Endoscopic therapy was associated with better clinical outcomes compared to pharmacological management in patients with peptic ulcer disease. These findings support the broader use of endoscopic treatment beyond emergency settings