Background: The promising prospects of proximal fibular osteotomy (PFO) as an alternative treatment of knee osteoarthritis (KOA), which has gained popularity in recent years, has yet to be systematically evaluated. Hence, this meta-analysis aims to critically assess the clinical and radiological outcome of PFO in the management of medial compartment KOA. Methods: Literature searches through PubMed, Scopus, CENTRAL, CINAHL, Google Scholar, and ProQuest databases were conducted, searching for eligible studies published from inception up to April 2020. Risk of bias assessments of randomized trials were performed via Cochrane RoB 2, while those of non-randomized studies with ROBINS-I tool. Random-effects model was utilized to estimate effect sizes. Results: A total of 907 patients and 1012 knees were included in this meta-analysis. PFO successfully ameliorated patients’ knee function (Hedges’ g 1.90; 95% confidence interval (CI) 1.62–2.18; I2 = 67%) and pain (visual analog scale: mean difference (MD) −4.13; 95% CI: −5.29 to −2.97), and also resulted in minimal complication rates, with peroneal nerve paresthesia being the most prevalent adverse event (5.93%; 95% CI: 2.15–11.25%), followed by peroneal nerve palsy (2.25%; 95% CI: 0.14–6.14%), fracture (0.56%; 95% CI: 0–1.74%), and recurrent deformity (0.54%; 95% CI: 0–1.74%). Furthermore, PFO was also associated with improved medial/lateral joint space ratio (MD 0.17; 95% CI: 0.15–0.19). Conclusion: PFO yielded promising prospects in the management of medial compartment KOA, as shown by substantial improvements in clinical and radiological outcomes. However, considering the low quality of evidence, further studies with more diverse populations and higher quality of body evidence are required to confirm these findings. © 2020 Elsevier B.V.