INTRODUCTION: A two-stage exchange arthroplasty is the standard management method of chronic periprosthetic joint infections (PJIs) of the hip in North America. However, a subset of patients become reinfected and may require a repeat two-stage exchange arthroplasty. The purpose of the present study was to assess revisions, reoperations, and risk factors for failure associated with repeat two-stage exchange arthroplasties for recurrent PJIs after total hip arthroplasty (THA). METHODS: We identified 52 repeat two-stage exchange THAs completed from 2000 to 2021 at a single, high-volume academic medical center. The mean age was 61 years, 39% were women, and the mean body mass index (BMI) was 33. At the time of the repeat two-stage exchange, high-dose antibiotic spacers were used in 90% of patients (28 articulating, 19 non-articulating), and 10% had a resection arthroplasty in the interim between stages. The mean time from repeat first stage to reimplantation was 33 weeks. Kaplan-Meier survivorship estimates were calculated, and risk factors (including the McPherson staging system) were assessed. At the final follow-up, 54% of patients were on chronic antibiotic therapy. The mean follow-up was six years. RESULTS: The 7-year survivorships free of re-revision for reinfection, any re-revision, and any reoperation were 85%, 57%, and 50%, respectively. The leading indications for re-revision were dislocation (45%) and PJI (35%). McPherson host grade C was a significant risk factor for re-revision for infection (HR [hazard ratio] 5, P = 0.04). Additionally, increased operative time at reimplantation was a risk for any reoperation (HR 1.06, P <
0.01) and reoperation for infection (HR 1.07, P <
0.01). At the final follow-up, 98% of patients had a revision THA in situ (one hip disarticulation). DISCUSSION: Repeat two-stage exchange arthroplasty of the hip had a 7-year survivorship free of re-revision for infection that was 85%, but only 57% were free of any re-revision (most due to revision for dislocation). McPherson C hosts had a 5-fold increased risk of re-infection.