Abstract Background Knee osteoarthritis (KOA) with varus alignment and medial space stenosis is a common degenerative disorder in the elderly. To reallocate the force bearing from the medial to the lateral compartment, the anti-varus osteotomy, including high tibial osteotomy (HTO) and proximal fibular osteotomy (PFO), corrects the mechanical lines of lower extremities using surgical methods, which alleviates the abrasion of medial cartilage and relieves pain. PFO is based on the “non-uniform settlement” theory. It is to cut small section of the proximal fibula, i.e., below the fibula head, which breaks the fibula and weakens its support for the lateral of the tibial plateau, lastly reduces the gap on the lateral side of the knee joint and offsets the knee varus deformity caused by weight bearing. We conducted this systematic review and meta-analysis to compare the clinical outcomes of PFO versus HTO intervention. Methods Twenty-three studies were acquired from PubMed, Embase, CNKI (China National Knowledge Infrastructure), Wanfang Database and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration’s Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess risk of bias. Results Twenty-three studies including 14 randomized controlled trials and 9 observational studies were assessed. The methodological quality of the trials ranged from low to high. The pooled results of the mean operation time (MD = − 38.75, 95% CI = − 45.66 to − 31.85, P < 0.00001), intraoperative bleeding (std. MD = − 4.12, 95% CI = − 5 to − 3.24, P < 0.00001), length of hospital stay (MD = − 3.77, 95% CI = − 4.98 to − 2.56, P < 0.00001) and postoperative complications (OR = 0.66, 95% CI = 0.37–1.18, P = 0.16) showed that the differences were statistically significant between the two interventions. The postoperative differences of visual analogue score (VAS) (MD = 0.15 95% CI = − 0.39 to 0.69, P = 0.58), hospital for Special Surgery knee score (HSS) (MD = − 2.68, 95% CI = − 6.30 to 0.94, P = 0.15), American knee society (AKS) score (MD = 0.04, 95% CI = − 0.69 to 0.77, P = 0.91), western Ontario and McMaster university of orthopedic index (WOMAC) (MD = 8.09, 95% CI = 2.06–14.13, P = 0.009) and femur–tibia angle (FTA) (MD = − 0.03, 95% CI = − 5.39 to 5.33, P = 0.99) were not statistically significant. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. Conclusions PFO and HTO have the same short-term efficacy in the treatment of KOA, but PFO can reduce the operation time, intraoperative bleeding, hospital stay and postoperative complications, which has certain advantages. Clinically, for patients with many complications and poor surgical tolerance, PFO can be preferred.