BackgroundWhen faced with a periprosthetic joint infection (PJI) following total knee arthroplasty, the treating surgeon must determine whether 2-stage revision or “liner exchange,” aka debridement, antibiotics, exchange of the modular polyethylene liner, and retention of fixed implants (DAIR), offers the best balance of infection eradication versus treatment morbidity. We sought to determine septic re-revision risk following DAIR compared to initial 2-stage revision. MethodsWe conducted a cohort study using data from Kaiser Permanente's total joint replacement registry. Primary total knee arthroplasty patients who went on to have a PJI treated by DAIR or 2-stage revision were included (2005-2018). Propensity score–weighted Cox regression was used to evaluate risk for septic re-revision. ResultsIn total, 1,410 PJIs were included, 1,000 (70.9%) treated with DAIR. Applying propensity score weights, patients undergoing DAIR had a higher risk for septic re-revision compared to initial 2-stage procedures (hazard ratio 3.09, 95% CI 2.22-4.42). Of DAIR procedures, 150 failed (15%) and went on to subsequent 2-stage revision (DAIR-F). When compared to patients undergoing an initial 2-stage revision, we failed to observe a difference in septic re-revision risk following DAIR-F (hazard ratio 1.11, 95% CI 0.58-2.12). ConclusionAlthough DAIR had a higher risk of septic re-revision, we failed to observe a difference in risk following DAIR-F when compared to those who initially underwent 2-stage revision. Functional outcome, patient, and organism factors are important to consider when discussing PJI management options. Level of EvidenceLevel III.