BACKGROUND: The practice of collecting various intraoperative tissue samples from diverse periarticular sites is essential for accurately identifying the responsible microorganism, making it the gold standard in the procedure for managing periprosthetic joint infection (PJI). We hypothesized that the location of positive intraoperative cultures differs significantly between patients who underwent septic revision following a one-stage exchange for hip PJI and those who did not. METHODS: We conducted a retrospective case-control study at our tertiary arthroplasty center, analyzing data from January 2009 to September 2017. Our search identified 56 patients who experienced septic failure following one-stage hip revision arthroplasty for PJI. These patients were matched 1:1 by age, sex, and surgery date with a control group who had successful one-stage revision total hip arthroplasty (THA) without septic failure. Positive intraoperative tissue samples were categorized into three locations: soft-tissue, bone-prosthesis interface (superficial bone), and deep bone (intramedullary). RESULTS: The septic failure cohort demonstrated a statistically significant increase in both the Charlson Comorbidity Index (CCI) and Body Mass Index (BMI) compared to the control group (P <
0.001 and P = 0.01, respectively). Furthermore, a significantly greater number of positive superficial and deep bone culture samples were identified within the septic failure group (P <
0.001 and P <
0.001, respectively). Additionally, regression analysis indicated that a positive deep bone culture is associated with nearly a three-fold increase in the odds of re-infection, with an odds ratio of 2.8 (95% confidence interval: 1.1 to 7.3, P = 0.031). CONCLUSION: A positive deep bone culture sample is significantly correlated with septic failure following a one-stage exchange for PJI of the hip. Patients exhibiting positive deep bone cultures may derive benefit from extended postoperative antibiotic therapy for the treatment of infection, as well as rigorous monitoring and evaluation of inflammatory markers during the follow-up phases subsequent to one-stage exchange arthroplasty.