Two-stage revision knee arthroplasty using an antibiotic-loaded spacer is the most widely performed procedure for infected knee arthroplasties. The clinical outcome of this type of surgery compared with aseptic joint revision with exchange of tibial and femoral components is still controversial. Therefore, we analyzed clinical outcomes of septic two-stage revisions compared with aseptic one-stage revision total knee arthroplasties (TKAs). In a retrospective study, we assessed 135 consecutive patients who underwent two-stage revision for septic TKA (52 patients) and one-stage aseptic total knee revision arthroplasty (83 patients). The average follow-up was 26.1 months for the aseptic group and 26.5 months for the septic group. For clinical evaluation, we used the Knee Society Score, Oxford Knee Score, Kujala score, Turba score, and the Short Form 36 (SF-36). Postoperative pain level was determined using the visual analog pain scale. The surgeries were performed 51 months (aseptic group) and 24 months (septic group) after primary TKA on average. The main indications for aseptic revision surgeries were instability (40%), aseptic loosening (22.4%), anterior knee pain due to pathologies of the patella (11.8%), or material wear (5.9%). In the clinical outcome, patients achieved 124.8 points in the aseptic group and 105.4 points in the septic group in the Knee Society Score. The Oxford Knee Score revealed 29.9 points for the aseptic group and 33.9 points for the septicgroup. For the Kujala score, we found 53.2 points in the aseptic group and 48.5 points in the septic group. For the Turba score, we found 8.4 points in the aseptic group and 10.8 points in the septic group. The SF-36 (psychical) showed 52.2 versus 49.5 points and the SF-36 (physical) showed 36.5 versus 35.4 points. Mean level of persisting pain on the visual analog scale was 3.0 (aseptic group) and 3.5 (septic group). Performing septic two-stage or aseptic one-stage tibial and femoral revision knee arthroplasty showed similar clinical outcomes in relation to objective and subjective outcome measures.