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(1) Background: Periprosthetic joint infection (PJI) can be managed with one- or two-stage revision surgery protocol. Despite several studies analyzing the eradication rates between both procedures, there are no comparative studies that analyze patient-reported outcome measures (PROMs) and quality-adjusted life years (QALYs) in both treatment strategies. (2) Methods: All patients who underwent a two-stage knee revision between January 2017 to December 2018, due to a periprosthetic joint infection were included in the study. From the time interval, we selected a comparative group with the one-stage septic procedure. All patients received the following questionnaires: Oxford Knee Score, EQ-5D-5L, SSQ-8, and the SF-36. Additionally, demographic patient data were collected. The quality-adjusted life years (QALY) were calculated using the EQ-5D-5L. (3) Results: A total of 35 patients with a mean age of 67.7 years (SD = 8.9) were included in the final evaluation. The mean follow-up period was 54.5 months (SD = 5.5). There was no statistically significant difference regarding the Charlson Comorbidity Index (CCI), postoperative complications, or all evaluated questionnaires. There was no statistically significant difference in QALYs between the one- and two-stage revision. (4) Conclusion: Our study results show that the one-stage revision for PJI achieves similar PROMs compared to two-stage revision.