Surgical antibiotic prophylaxis is one of the most useful measures to prevent surgical wound infection. OBJECTIVE: The aim of this project is to evaluate the appropriateness of the use of antibiotic prophylaxis in surgical procedures performed in Spanish hospitals, both globally and according to the type of surgery performed. METHOD: For this purpose, an observational, retrospective, cross-sectional, and multicentre study has been designed to collect all the variables that allow the evaluation of the appropriateness of surgical antibiotic prophylaxis by comparing the prescribed treatment, the recommendations included in the local guidelines, and the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology and the Spanish Association of Surgeons. Indication, choice of antimicrobial, dose, route and duration of administration, timing, re-dosing, and duration of the prophylaxis will be taken into account. The sample will consist of patients who underwent scheduled or emergency surgery, either as inpatients or outpatients, in hospitals in Spain. A sample size of 2335 patients has been established to estimate, with 95% confidence and 80% power, a percentage of appropriateness that is expected to be around 70%. Differences between variables will be analysed using Student's t-test, Mann-Whitney U test, Chi-square test, or Fisher's test, as appropriate. The degree of agreement between the antibiotic prophylaxis recommended by the guidelines of the different hospitals and that recommended in the literature will be analysed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalised linear mixed models will be performed to identify possible factors associated with differences in the appropriateness of antibiotic prophylaxis. DISCUSSION: The results of this clinical study will allow us to focus on specific surgical areas with higher rates of inappropriateness, identify key points of action and guide future strategies for antimicrobial stewardship programs in the area of antibiotic prophylaxis.