Background: The correction of lower limb deformity should be performed at the site of deformity to maintain knee joint orientation. However, the effectiveness of open-wedge high tibial osteotomy (OWHTO) for treatment of medial osteoarthritis in varus malalignment without definite tibial varus deformity has not been confirmed. Purpose/Hypothesis: This study aimed to compare the clinical and radiologic outcomes after OWHTO in patients without tibial varus deformity versus patients with tibial varus deformity after matching for confounding factors. We hypothesized that these outcomes would be inferior in patients without tibial varus deformity. Study Design: Cohort study; Level of evidence, 3. Methods: The outcomes of 133 OWHTO operations for medial osteoarthritis in 107 patients were retrospectively reviewed after follow-up for >2 years. The patients were divided into group 1 (tibia with varus deformity, preoperative medial proximal tibial angle [MPTA] <85°) and group 2 (tibia without varus deformity, preoperative MPTA ≥85°). The confounding factors, including patient characteristics, preoperative limb alignment, degree of osteoarthritis, and correction angle, were matched using propensity score matching. The radiologic parameters, including MPTA and joint line obliquity, were evaluated preoperatively, between 6 and 12 months postoperatively, and at the last follow-up. The radiologic outcomes were assessed using the medial joint space width and mechanical hip-knee-ankle angle. The clinical outcomes were evaluated by the Hospital for Special Surgery knee score, Knee Society Score (KSS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. The clinical and radiologic outcomes were compared between the groups. The proportions of patients achieving improvement in the clinical outcome beyond the minimal clinically important difference (MCID) or minimally important change were compared between the groups. Results: After propensity score matching, 32 patients were selected for each group. The mechanical hip-knee-ankle angle was corrected without significant difference from a mean ± SD varus angle of 8.0°± 3.3° to valgus angle of −3.2°± 2.5° in group 1 and from varus 8.0°± 3.6° to valgus −3.9°± 1.7° in group 2. The preoperative joint line obliquity was greater in group 2 as compared with group 1 (2.2°± 2.2° vs −0.4°± 1.8°, P < .001). With a similar 10° correction angle, the postoperative MPTA and joint line obliquity were 96.6°± 2.5° and 5.3°± 2.3°, respectively, in group 2, which were greater than 94.0°± 2.6° and 3.5°± 1.8°, respectively, in group 1 (both P < .001). The changes in joint space width and mechanical hip-knee-ankle angle were not significantly different between the groups over the follow-up period. At the last follow-up, the postoperative KSS objective score and WOMAC pain score in terms of symptom improvement were not significantly different between groups (P = .092 and .068). However, the postoperative KSS and WOMAC functional scores were significantly worse in group 2 than in group 1 (77.3 ± 14.1 vs 84.4 ± 11.6, P = .044; 10.3 ± 9.2 vs 5.6 ± 7.2, P = .001). In group 1, 96.9% and 100% of patients showed improvements of >10 points in the KSS functional score and 15 points in the WOMAC functional score based on MCID or minimally important change. Meanwhile, 65.6% and 81.3% of patients in group 2, which were significantly lower than those of group 1, were improved beyond the MCID or minimally important change (P = .001 and .024, respectively). Conclusion: In varus malalignment, the knee joint line was more oblique in patients without tibial varus deformity after OWHTO pre- and postoperatively. The clinical outcomes in terms of functional scores were inferior in patients without tibial varus deformity. However, the radiologic outcomes and symptomatic improvement after OWHTO were comparable regardless of the preoperative tibial varus deformity on midterm follow-up.