Fifty-six patients with stage II-B osteosarcoma around the knee were followed-up for a minimum of 92 months. The percentage of tumour cells expressing VEGF/MMP-9 was assessed using immunohistochemistry. The relationship between VEGF/MMP-9 expression and survival was assessed using Kaplan-Meier and Cox regression models. Patients with tumours expressing VEGF in >25% of their cells had shorter overall (p=0.019) and disease-free survival (p=0.009). Patients with tumours expressing MMP-9 had shorter overall (p=0.0042) and disease-free survival (p=0.0004). There was an association between VEGF and MMP-9 expression (p=0.021). The negative effects of VEGF/MMP-9 expression on survival were independent of traditional prognostic factors.