The aim of this study was to evaluate which lower extremity alignment (knee and ankle joint) parameters affect knee joint line obliquity (KJLO) in the coronal plane after open wedge high tibial osteotomy (OWHTO). Overall, 69 knees of patients that underwent OWHTO were evaluated using radiographs obtained preoperatively and from 6 weeks to 3 months postoperatively. We measured multiple parameters of knee and ankle joint alignment (hip-knee-ankle angle [HKA], joint line height [JLH], posterior tibial slope [PS], femoral condyle-tibial plateau angle [FCTP], medial proximal tibial angle [MPTA], mechanical lateral distal femoral angle [mLDFA], KJLO, talar tilt angle [TTA], ankle joint obliquity [AJO], and the lateral distal tibial ground surface angle [LDTGA]; preoperative [-pre], postoperative [-post], and the difference between -pre and -post values [-Δ]). We categorized patients into two groups according to the KJLO-post value (the normal group [within ± 4 degrees, 56 knees] and the abnormal group [greater than ± 4 degrees, 13 knees]), and compared their -pre parameters. Multiple logistic regression analysis was used to examine the contribution of the -pre parameters to abnormal KJLO-post. The mean HKA-Δ (-9.4 ± 4.7 degrees) was larger than the mean KJLO-Δ (-2.1 ± 3.2 degrees). The knee joint alignment parameters (the HKA-pre, FCTP-pre) differed significantly between the two groups (p < 0.05). In addition, the HKA-pre (odds ratio [OR] = 1.27, p = 0.006) and FCTP-pre (OR = 2.13, p = 0.006) were significant predictors of abnormal KJLO-post. However, -pre ankle joint parameters (TTA, AJO, and LDTGA) did not differ significantly between the two groups and were not significantly associated with the abnormal KJLO-post. The -pre knee joint alignment and knee joint convergence angle evaluated by HKA-pre and FCTP-pre angle, respectively, were significant predictors of abnormal KJLO after OWHTO. However, -pre ankle joint parameters were not significantly associated with abnormal KJLO after OWHTO.