OBJECTIVES: To determine whether the serum vascular endothelial growth factor (VEGF) level in patients with urothelial cancer could be used as a predictor of recurrence and disease progression. METHODS: Serum levels of VEGF in 51 healthy controls and 135 patients with urothelial cancer (81 superficial and 54 invasive cancers) were measured using a sandwich enzyme immunoassay, and the results were analyzed with respect to several clinicopathologic factors. RESULTS: Significant differences in the serum VEGF level were observed between healthy controls and patients with superficial urothelial cancer (34+/-12 pg/mL versus 49+/-27 pg/mL, P<0.001) and between healthy controls and patients with invasive cancer (34+/-12 pg/mL versus 51+/-35 pg/mL, P<0.001), whereas there was no significant difference in the serum VEGF level between superficial and invasive cancers (49+/-27 pg/mL versus 51+/-35 pg/mL, P = 0.31). Among patients with superficial cancer, the disease-free survival rate of patients with elevated serum levels of VEGF was significantly lower than that of patients with normal levels (P<0.05). The progression-free survival rate of superficial cancer patients with elevated serum levels of VEGF was also significantly lower than that of patients with normal levels (P<0.01). In addition, Cox's multivariate analysis revealed that the elevation of serum VEGF level was strongly associated with disease-free survival and progression-free survival in patients with superficial cancer (P<0.05). CONCLUSIONS: The results of this study suggest that the elevation of serum VEGF level could be used as a new independent predictor of recurrence and disease progression in patients with superficial urothelial cancer.