Introduction: Inappropriate use of antibiotics is one of the main causes of the emergence of antibiotic resistance in sub-Saharan Africa. To contribute to better antibiotic prescribing, the aim of this work was to evaluate prescribing in the surgery and surgical specialties department at the University Hospital Center Yalgado Ouedraogo (CHU-YO). Methods: This was a prospective cross-sectional study from December 15 to 21, 2021. Patients hospitalized in the surgical department were included. Compliance guidelines were the recommendations of the SFAR and the guide to good antibiotic prescribing in Burkina Faso. Results: A total of 162 patients were hospitalized during the study period, of whom 97 were included. The prevalence of antibiotic prescriptions was 59.9%. Curative antibiotic therapy accounted for 66% of prescriptions, while all surgical patients received antibiotic prophylaxis. The β-lactam family was prescribed in 88.5% of cases for prophylaxis and 91.3% for curative treatment. Ceftriaxone was prescribed in 71.3% of cases for prophylaxis and 44.9% for curative antibiotic therapy. Overall compliance was 22.3% for antibiotic prophylaxis and 49.3% for antibiotic therapy. Non-compliance with antibiotic prophylaxis was linked to an inappropriate choice of antibiotic for prophylaxis, and to unjustified prescribing for antibiotic therapy. Conclusion: Capacity-building for prescribers and the development of guidelines could help improve the appropriateness of antibiotic use at CHU-YO.