Culture negative prosthetic joint infections (PJI) still remain an issue even the advantages in PJI diagnosis. This is the reason why some orthopedic surgeons fear to use preoperative antibiotic prophylaxis when a PJI is suspected. The purpose of the present study was to evaluate the influence of preoperative antibiotic prophylaxis in intraoperative cultures An enhanced diagnostic protocol for PJI (Zimmerli criteria) was used for the inclusion criteria in order to collect all PJI accounted in a University Hospital. Patients were prospectively randomized in two groups. The control group received the classical preoperative antibiotic prophylaxis. The study group did not receive prophylaxis prior to surgery There were 14 patients in each group. They correspond to 13 infections of total hip arthroplasty (THA), 12 infections of total knee arthroplasty (TKA) and 3 reverse shoulder prosthesis (RSA) infections. There were 10 patients in the study group and 10 patients in the control group with at least one positive microbiological criterion. There were 8 patients in each group with culture negative PJI (p>0.05) Preoperative antibiotic prophylaxis does not affect intraoperative cultures in suspected or confirmed PJI. Therefore it is essential to deliver antibiotic prophylaxis in any patient in which prosthesis is to be implanted in order to protect the prosthesis from infection