Background: Some patients undergoing a 2-stage revision for a periprosthetic joint infection require a repeat spacer in the interim (removal of existing spacer with insertion of a new spacer or spacer exchange) due to persistent infection. The objectives of this study are to (1) determine the factors associated with patients who receive a repeat spacer and (2) compare the infection-free survival (overall and stratified by joint type) of reimplantation in patients who did or did not receive a repeat spacer. Methods: From 2001 to 2014, 347 hip or knee 2-stage revisions that finally underwent reimplantation and had a minimum 2-year follow-up were identified. An interim spacer exchange was performed in 59 (17%) patients (exchange cohort). Patient-related and organism-related factors were compared between the exchange and non-exchange cohorts. Kaplan-Meier survival curves were performed to assess the success (absence of signs of infection, reoperation for infection, periprosthetic joint infection-related mortality) of both cohorts. Results: Patients in the exchange group had higher comorbidity score (P = .020), prolonged time to reimplantation (P < .001), and higher prevalence of resistant organisms, though not statistically significant (P = .091). The 5-year infection-free survival rates were 64% (knee 62%, hip 64%) in the exchange cohort, and 78% (knee 77%, hip 78%) in the non-exchange cohort (P = .020). Conclusions: Patients requiring an interim spacer exchange were found to have more comorbidities, prolonged treatment period, and were more likely to be infected with a resistant organism. About one-third of such patients became reinfected within 5 years compared to only one-fifth of the patients without an interim spacer exchange. (C) 2018 Elsevier Inc. All rights reserved.