Abstract： Objective To compare the clinical efficacy of gemcitabine arterial infusion chemotherapy with intravenous chemotherapy in the management of patients with advanced pancreatic cancer and to evaluate the efficacy and safety of gemcitabine arterial infusion chemotherapy. Methods 43 patients with advanced pancreatic cancer were included in this study, of whom 21 patients received arterial infusion chemotherapy (Group A) and the other 22 were treated by intravenous chemotherapy (Group B), gemcitabine combined with 5-FU chemotherapy was administrated in both groups. The main outcomes were clinical benefit response (CBR), tumor response rate and toxicity. Results Compared with Group B, there was a significant improvement of CBR in group A (81% vs 50%, P =0.033) ; there was also significant improvement of pain control in group A (76.2% vs 45.5%, P =0.039). There was no significant difference in the tumor response rate between two groups (33.3% vs 22.7%, P =0.498). No significant increase of side effects was observed in both groups. Conclusions In the management of advanced pancreatic cancer, the arterial infusion method may be more favorable than intravenous approach in improving clinical benefits with mild toxicity and well tolerability.