BACKGROUND: Acid-suppressive therapy (AST) is often used without proper assessment of the need, dosage, or duration of treatment. This inappropriate use can lead to significant side effects, harmful drug interactions, and increased healthcare costs for patients. OBJECTIVE: This study aimed to evaluate stress ulcer prophylaxis (SUP) among hospitalized adult patients who were non-critically ill. METHOD: This hospital-based, retrospective cross-sectional study was conducted in general internal medicine wards at Atbara Teaching Hospital, Sudan, from September to December 2024. The study included all hospitalized adult patients who received AST for SUP. RESULTS: In total, 221 patients were evaluated in this study; among them, 136 (61%) were males and 75 (34%) were aged 61–80 years. Overall, only 84 patients (38%) were eligible for SUP, with pantoprazole 214 (97%) and intravenous (IV) route 215 (97.3%) being the most commonly used. Anticoagulant 48 (22%) and steroid or NSAID 20 (9%) use were the most and least the common risk factors based on ASHP criteria, respectively. A statistically significant association was found with polypharmacy ( < 0.001); 116 (52%) had polypharmacy, of whom 80 (69%) were eligible for SUP, and significant associations were also identified with other clinical characteristics, such as past medical history ( < 0.001) and sepsis ( = 0.013). CONCLUSION: This study revealed a high rate of inappropriate SUP prescriptions among non-ICU patients in a Sudanese hospital, with IV pantoprazole being the most used. These findings emphasize the need for evidence-based protocols, greater clinical pharmacist involvement, and interdisciplinary efforts to improve the appropriateness and cost-effectiveness of SUP use.