Backgroud: Patients with alpha-fetoprotein (afp)–producing gastric cancer have a high incidence of liver metastasis and poor prognosis. There is some controversy about clinical manifestations in these patients. Methods: Our study enrolled patients who, before surgery, had gastric cancer with serum afp exceeding 20 ng/mL [afp>20 (n = 58)] and with serum afp 20 ng/mL or less [afp≤20 (n = 1236)]. Clinical manifestations were compared between the groups. Results: Early gastric cancer was more frequent (30.1% vs. 4%) and advanced gastric cancer was less frequent (69.9% vs. 96%) in the afp≤20 group than the afp>20 group (p < 0.001). Liver and lymph node metastasis occurred less frequently in the afp≤20 group (4.4% vs. 27.6%, p < 0.001, and 60.7% vs. 91.4%, p < 0.001, respectively). The 1-, 3-, 5-, and 10-year survival rates of afp≤20 patients were 75.2%, 53.4%, 45.8%, and 34.6% respectively. The 1-, 3-, 5-, and 10-year survival rates of patients with afp greater than 20 ng/mL, but 300 ng/mL or less, were 46.7%, 28.9%, 17.8%, and 13.3% respectively. The 1-, 3-, and 5-year survival rates of patients with serum afp greater than 300 ng/mL were 15.4%, 7.7%, and 0% respectively. The independent predictors for survival time were afp concentration, age, peritoneal seeding, liver metastasis, lymph node metastasis, vascular invasion, TNM stage, curative surgery, serosal invasion, and Lauren classification. Conclusions: Patients with high serum afp had a high frequency of liver and lymph node metastasis and very poor prognosis. More aggressive management with multimodal therapy (for example, chemotherapy, radiotherapy) might be needed when treating such patients.