The purpose of this prospective study was to evaluate the therapeutic effects of intra-arterial chemotherapy in preventing high-risk superficial bladder cancer from recurrence and progression. from may 2003 to December 2007, 52 patients were divided randomly into 2 groups. Twenty-five patients were given intra-arterial chemotherapy with gemcitabine and cisplatin, and 27 patients received intravesical instillation with epirubicin. After 6-67 months of follow-up (median, 40 months), the overall recurrence-free rates of the intra-arterial chemotherapy and intravesical instillation groups were 83.3% and 33.4%, respectively (p=0.001 log rank). Tumor progression was not found in the intra-arterial chemotherapy group while 7 patients in the intravesical instillation group had tumor progression. The overall tumor progression-free rates were 100% and 58.5%, respectively (p=0.009 log rank). The patients with functional bladders were 100% and 81.5% in the intra-arterial chemotherapy and intravesical instillation groups after 67 months of follow-up, respectively. In conclusion, intra-arterial chemotherapy is more effective than intravesical instillation in preventing high-risk superficial bladder cancer from recurrence and progression.