Background and aimDifferent authors have demonstrated the usefulness of the histological analysis in the diagnosis of prosthetic joint infection; however, its clinical validity is still controversial. The aim of this article is to describe and analyze the clinical validity of histological analysis in the diagnosis of prosthetic infection in patients undergoing hip or knee prosthetic replacement. Material and methodsWe present a retrospective study including 133 hip and knee prosthetic replacements performed in our center between 2008 and 2020. A descriptive, bivariate statistical analysis was performed and the clinical validity of the histological analysis was determined. OutcomesThe clinical validity of the intraoperative histology offered a sensitivity of 48%, a specificity of 91%, a positive predictive value of 55% and a negative predictive value of 88%. ConclusionsThe determination of the clinical validity of histological analysis shows a high specificity. This analysis is an appropriate diagnostic tool for detecting healthy patients, with no infection.