Protein-bound polysaccharide K (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor. Several clinical studies have demonstrated that PSK has antitumor properties. In Japan, PSK has been used as an adjuvant chemotherapeutic drug against gastric cancer. However, there is little evidence about the effectiveness of PSK in clinical practice. The aim of this study was to evaluate the impact of PSK on postoperative recurrence in patients with gastric cancer. The patients with Stage II/III gastric cancer who underwent a surgical curative resection between 1999 and 2008 at the Department of Surgical Oncology, Osaka City University were included in this retrospective study. All patients received oral fluorinated pyrimidine anti-metabolites with or without PSK after surgical operation. We analyzed clinicopathological features and evaluated the impact of PSK on postoperative recurrence. One hundred thirty eight patients received oral anti-metabolized alone (control group) and 116 patients received PSK (PSK group). No significant difference between control and PSK group in relapse free survival was detected. In PSK group, venous invasion was an independent factor for postoperative recurrence (p=0. 004, HR 1. 538, 95% CI 1. 152 to 2.054). Our results suggested that a population with venous infiltration of primary lesion should be at risk of recurrence after surgery even if PSK was administered as postoperative adjuvant therapy.