Objective To evaluate the efficacy of preoperative regional intra-arterial chemotherapy (RIAC) in the treatment of resectable pancreatic head carcinoma. Methods The clinical data of 50 patients with resectable pancreatic head carcinoma who had been admitted to the Research Institute of Pancreatic Diseases of Fudan University from December 2006 to July 2007 were retrospectively analyzed. Patients were randomly divided into2 groups (n =25 in each group): patients in group A were treated with preoperative RIAC followed by regional pancreaticoduodenectomy, and patients in group B were treated with surgical procedure routinely. The lymphatic metastases in the 50 specimens of pancreatic head carcinoma were detected by histological examination with hematoxylin and eosin (HE) staining, and lymphatic micrometastases were detected by immunohistochemical method with staining of cytokeratin AE1/AE3 in 10 specimens with negative HE staining of the lymph nodes in each group. Results There was no significant difference in the incidence of complications, the length of hospital stay and the 1-, 2-year survival rates between the 2 groups (χ2 = 0.12, 2.88, P > 0.05). The incidence of positive lymph node metastasis in group A was 7.1% (52/734), which was significantly higher than 22.1% (118/532) in group B (χ2 = 60.01, P < 0.05). The incidence of lymphatic micrometastasis was 9.4% (30/319) in group A, and 9.1% (23/252) in group B, with no statistical difference between the 2 groups (χ2= 0.01, P > 0.05). Conclusions Preoperative RIAC is helpful in improving the prognosis of patients with resectable pancreatic head carcinoma by reducing the incidence of lymphatic metastasis and decreasing tumor stage.