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Background: Proximal tibial osteotomy (PTO) is a well-established treatment for coronal deformity and focal cartilage defects. However, the utility of joint-preserving interventions must be weighed against potential effects on subsequent total knee arthroplasty (TKA). The purpose of this study was to determine the effect of PTO on subsequent TKA by comparing outcomes in patients with bilateral TKAs following unilateral PTO., Methods: Patients who underwent bilateral TKAs from 2000 to 2015 at a single institution and had previously undergone a unilateral valgus-producing PTO were reviewed. We evaluated 140 TKAs performed in 70 patients (24 female, 46 male) with a mean age at PTO of 50 ± 8 years. The patients underwent conversion to TKA at a mean of 14 ± 7 years following ipsilateral PTO and were followed for a mean of 25 ± 7 years (range, 6 to 40 years) following PTO. The Knee Society Score (KSS), Forgotten Joint Score-12 (FJS-12), subjective knee preference, and revision were compared between the PTO-TKA and contralateral TKA-only sides., Results: The PTO side demonstrated similar KSS Knee subscores (41 ± 16) compared with the contralateral side (39 ± 16, p = 0.67) immediately prior to arthroplasty. Patients had significant improvements in KSS (p < 0.001) after TKA, with clinically similar KSS values at 2 to 15 years of follow-up when knees were compared in a pairwise fashion (p = 0.10 to 0.83). Five PTO-TKA knees (7%) and 4 control TKA-only knees (6%) underwent revision at a mean of 5 years postoperatively (p = 0.76). The number of all-cause reoperations was approximately twice as high in PTO-TKA knees (13% compared with 6% in TKA-only knees, p = 0.24). At the time of final follow-up, PTO-TKA knees demonstrated similar FJS-12 scores (72 ± 26) compared with the contralateral knees (70 ± 28, p = 0.57). Nineteen percent of patients preferred the PTO-TKA knee, 19% preferred the contralateral TKA-only knee, and 62% stated that their knees were equivalent (p > 0.99). The final Tegner activity score was 2.5 ± 1.4., Conclusions: Long-term clinical function of TKA following PTO was excellent, with patients demonstrating comparable subjective outcomes and equivalent knee preference compared with the contralateral TKA-only knees. Further, well-matched studies are needed to evaluate long-term revision and reoperation rates following PTO-TKA., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G870)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)