Objective: The aims of this study were (1) to investigate the changes in the serum concentration of prophylactically administrated vancomycin in the perioperative period of revision hip arthroplasty in penicillin/cephalosporin-allergic patients, (2) to assess whether thepostoperative re-administration of vancomycin is needed, and (3) to determine the relationships of vancomycin serum concentration withblood loss, body weight, and fluid replacement in such patients.Methods: This study consisted of 29 patients (20 females, 9 males; mean age=63.3 years; age range=45-79 years) with a history of penicillin/cephalosporin allergy undergoing revision hip arthroplasty secondary to aseptic loosening or periprosthetic fractures. Serum vancomycinlevels were measured (1) before administration of vancomycin, (2) at the time of skin incision, (3) every 1,5 hours thereafter until the endof the operation, (4) during the skin closure, and (5) after three and 12 hours from the initial dosage. Data regarding body weight, amountsof intraoperative blood loss, fluid and blood replacements and postoperative wound drainage were recorded.Results: The average blood loss, fluid replacement, and drain volume were 1280.3±575.8 (500-2700) mL, 2922.6±768.8 (1700-4600) mL,and 480.2±163.7 (200-850) mL, respectively. The mean levels of serum vancomycin were 46.3±21.8 (14.1-80.7) mg/L at the time of skinincision, 17.9±4.7 (9.4-30.9) and 9.8±2.2 (4.3-13.8) mg/L after 1.5 and 3 hours from the beginning of the surgery and 5.1±1.1 (2.9-6.8)mg/Lafter 12th hour postoperatively. The measured vancomycin levels were below the effective serum concentrations (< 5 mg/L) for 18 patients at 12 hours the administration of the first dose. A moderate level negative correlation between the blood loss/body weight ratio andvancomycin levels was found (p=0.004, r=-0.493). Predictive ROC curve analysis resulted in determining a blood loss volume higher than1150 ml and a blood loss/body weight ratio higher than 18,5 is significant to estimate the vancomycin level below the minimum effectiveserum level at 12th hour postoperatively (AUC=0.793±0.16, p=0.009, AUC=0.753) 26±0.12, p=0.025, respectively).Conclusion: Evidence from this study has indicated vancomycin concentration at 12th hour is below the effective level in most patients.Thus, earlier repetitive infusion of vancomycin seems to be necessary in penicillin/cephalosporin-allergic patients undergoing revisionhip arthroplasty, especially in those with high blood loss.Level of Evidence: Level III, Therapeutic Study