Aim of the work: To investigate the vascular endothelial growth factor (VEGF) levels in serum and synovial fluid of patients with knee osteoarthritis (KOA) and to determine the relationship of VEGF levels with clinical manifestation, physical function, radiographic grading and ultrasonography (US) findings. Patients and methods: 45 patients with KOA and 15 matched control subjects were enrolled. Western Ontario McMaster Osteoarthritis index (WOMAC) was scored, knee X-rays assessed using Kellgren and Lawrence (KL) scale and superficial gray scale and colour Doppler US were done. Serum and synovial VEGF levels were analyzed. Results: The 45 patients mean age was 56.5 ± 11.2 years; 39 females and 6 males (F:M 6.5:1). 30 (66.7%) patients had bilateral symptomatic KOA. Knee effusion was mild in 4, moderate in 26 and severe in 21. The mean WOMAC score was 70.9 ± 10.7; pain (14.7 ± 3.4); stiffness (6.2 ± 1.4) and disability (49.2 ± 12.4). The serum VEGF level was 0.29 ± 1.02 pg/ml and the synovial 0.48 ± 0.1 pg/ml both significantly increased compared to the control (0.14 ± 0.7 pg/ml and 0.33 ± 0.1 respectively, p < 0.0001). Levels in grade 3 KL were significantly increased compared to those with grades 1 or 2 (p < 0.0001) and between colour Doppler US grades 1 and 2 (p < 0.0001). A strong correlation was present between serum and synovial VEGF with X-ray and colour Doppler US grading as well as the WOMAC index (p < 0.0001). Conclusion: Serum and synovial VEGF correlated with clinical, functional, radiographic and US severity in KOA patients. Both VEGF and musculoskeletal ultrasound may serve as promising potential tools for evaluating disease severity in KOA.