BACKGROUND: Although 2-stage exchange arthroplasty is the preferred surgical treatment for periprosthetic joint infection (PJI) in the United States, little is known about the risk of complications between stages, mortality, and the economic burden of unsuccessful 2-stage procedures. METHODS: The 2015-2019 Medicare 100% inpatient sample was used to identify 2-stage PJI revisions in total hip and knee arthroplasty patients using procedural codes. We used the Fine and Gray sub-distribution adaptation of the conventional Kaplan-Meier method to estimate the probability of completing the second stage of the 2-stage PJI infection treatment, accounting for death as a competing risk. Hospital costs were estimated from the hospital charges using "cost-to-charge" ratios from Centers for Medicare and Medicaid Services. RESULTS: A total of 5094 total hip arthroplasty and 13,062 total knee arthroplasty patients had an index revision for PJI during the study period. In the first 12 months following the first-stage explantation, the likelihood of completing a second-stage PJI revision was 43.1% (95% confidence interval [CI] 41.7-44.5) for hips and 47.9% (95% CI 47.0-48.8) for knees. Following explantation, 1-year patient survival rates for hip and knee patients were 87.4% (95% CI 85.8-88.9) and 91.4% (95% CI 90.6-92.2), respectively. The median additional cost for hospitalizations between stages was $23,582 and $20,965 per patient for hips and knees, respectively. Hospital volume, Northeast or Midwest region, and younger age were associated with reduced PJI costs (P < .05). CONCLUSION: Although viewed as the most preferred, the 2-stage revision strategy for PJI had less than a 50% chance of successful completion within the first year, and was associated with high mortality rates and substantial costs for treatment failure.