Background: In carefully selected patients with an arthritic valgus knee, distal femoral osteotomy (DFO) can improve symptoms at medium- to long-term follow-up, reducing osteoarthritis progression. To date, there is no clear evidence in the current literature regarding the role of postoperative joint line obliquity (JLO) in valgus deformity correction. Purpose: To assess the clinical and radiological outcomes of medial closing-wedge DFO (MCW-DFO) for the treatment of valgus knees, considering both tibial- and femoral-based deformities, as well as to verify the efficacy and safety of MCW-DFO according to JLO boundaries (≤4°). Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis was conducted on a cohort of patients with valgus knees. Patients were divided into 2 groups: femoral-based valgus (FB-V) and tibial-based valgus (TB-V). Knee radiographs were collected before surgery and at the last follow-up. The clinical outcome was evaluated through several validated scores (International Knee Documentation Committee, Knee Society Score, Knee injury and Osteoarthritis Outcome Score, Tegner, Numeric Rating Scale, Crosby-Insall). Results: A total of 30 patients (34 knees) with a mean age of 49.3 ± 9.1 years were included in the study. The overall mean follow-up was 9.4 ± 5.9 years. The mean preoperative hip-knee-ankle angle was 187.6°± 3.3° (range, 181.5°-191°) and the postoperative angle was 180°± 3.1° (range, 176°-185°). Most postoperative JLOs were within the safe zone of ≤4° in both groups (the postoperative JLO was >4° in 4 patients in the TB-V group and 1 patient in the FB-V group), although FB-V knees exhibited significant superior JLO correction (postoperative JLO in the TB-V group: mean, 4.0°± 2.5° [P = .1]; postoperative JLO in the FB-V group: mean, 2.4°± 1.4° [P = .5]). Significant improvements in all clinical scores were observed in both groups (P < .01). Additionally, the severity of the osteoarthritis did not worsen at the last follow-up. Conclusion: MCW-DFO is an effective procedure for treating pathological valgus knees, regardless of the site of the deformity. Both FB-V and TB-V groups showed comparable improvements in the clinical scores, development of osteoarthritis, and the restoration of a neutral mechanical axis. Notably, FB-V knees achieved more JLO correction compared with the TB-V ones.