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Background: Periprosthetic joint infection (PJI) is the leading cause of early revisions after total knee arthroplasty. Debridement, antibiotics, and implant retention (DAIR) procedures are often the initial treatment for PJI. However, there is concern that failed DAIR undermines the future success of revision procedures. This study aims to investigate the impact of DAIR on the success of subsequent staged revisions for PJI. Methods: A multicenter retrospective review was performed over a 15-year period. Treatment success was defined as implant retention without the use of long-term suppressive antibiotics. This was compared between patients who underwent a staged revision as the first procedure for PJI (staged-only) and patients who failed DAIR before staged revision (F-DAIR). Competing risk survival analysis was performed to compare the 2 groups and considered for patient demographics, American Society of Anesthesiologists score, organism type, body mass index, age of prosthesis, and duration of symptoms. Results: Of 291 eligible patients, 63 underwent staged revision and 228 underwent DAIR as the first procedure for PJI. Of the 228 DAIR patients, 75 failed DAIR and underwent subsequent staged revision (F-DAIR). At mean follow-up of 6.2 years, the success rate was 72% in the F-DAIR group and 81% in the staged-only group. On survival analysis, there was no significant difference in subdistribution hazard ratio comparing the probability of failure (implant retention) in the 2 treatments groups (subdistribution hazard ratio = 0.72; 95% confidence interval 0.32-1.61; P = .42). Conclusion: This study suggested that a previously failed DAIR does not compromise the success rate of a subsequent staged revision.