We studied retrospectively the clinicopathological features of gastric cancer with duodenal invasion and compared these with those with non-invasion, to investigate the prognostic significance of duodenal invasion. The patients were grouped into two groups of Group A (65 patients) with duodenal invasion and Group B (197 patients) without invasion who underwent gastrectomy for advanced distal gastric carcinoma according to histological findings. In Group A, many were at high age and with symptoms of pyloric stenosis. Group A (91%) had a significantly higher incidence of serosal invasion and infiltration into the pancreas head than did Group B (76%) (p < 0.01). In N3 metastasis, there was a significant difference between Group A (60%) and Group B (36%) (p < 0.01). The five-year-survival rate in Group A was 14.0% and in Group B was 43.3% (p < 0.001). In cases of duodenal invasion, patients with symptoms of pyloric stenosis demonstrated a poorer prognosis than those without. Those with longer than 20 mm invasion had a significantly higher incidence of N3 metastasis than those with less than 10 mm (p < 0.05). Lymphangitic type had longer invasive length to duodenum, and N3 metastasis of the lymphangitic type was frequent comparing to localized type (42%) and invasive type (47%) (p < 0.001) (95%) (p < 0.01). These results showed that duodenal invasion was a significant prognostic factor in cases of distal gastric carcinoma. In the therapeutic strategy for advanced gastric carcinoma with duodenal invasion, it is necessary to perform gastrectomy with regional lymph nodes dissection and with combined resection of adjacent organs.