High tibial osteotomy (HTO) modifies the mechanics of the affected knee but can also affect the nonoperated knee. However, no research has reported on the prognosis and risk factors related to the nonoperated knee after unilateral HTO. To assess the radiological parameters associated with osteoarthritis (OA) progression and the need for surgery in the nonoperated knee after unilateral HTO, with concurrent assessment of the operated knee. Case series; Level of evidence, 4. The medical charts of 197 patients with knee OA who underwent unilateral HTO between March 2007 and December 2020 were retrospectively investigated. Radiological parameters such as the Kellgren-Lawrence grade, weightbearing line ratio, joint line convergence angle (JLCA), and joint line obliquity angle were assessed preoperatively and 1 year postoperatively. The mean follow-up length for the 197 patients was 5.9 ± 3.2 years for the operated knee and 5.5 ± 3.2 years for the nonoperated knee. A smaller postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .027) and undergoing surgery (P = .006) in the nonoperated knee. Conversely, a larger postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .014) and conversion to arthroplasty (P = .027) in the operated knee. A postoperative JLCA >1.5° (P < .001) and <3.9° (P < .001) was needed to reduce the risk of undergoing surgery in the nonoperated knee and OA progression in the operated knee, respectively. Additionally, a pre- to postoperative change in the JLCA (ΔJLCA) between -5.6° and -1.7° (P = .021 and P = .004, respectively) was needed to reduce the risk of OA progression in both knees. A large medial joint opening (a small postoperative JLCA) in the operated knee after unilateral HTO was associated with a higher risk of OA progression and surgery in the nonoperated knee. Conversely, a small medial joint opening (a large postoperative JLCA) was associated with a higher risk of OA progression and conversion to arthroplasty in the operated knee. For a balanced medial joint opening, if the postoperative JLCA was between 1.5° and 3.9° or the ΔJLCA was between -5.6° and -1.7°, a favorable prognosis in both knees could be anticipated.