OBJECTIVE: To explore the value of superior mesenteric vein (No.14v) lymph node dissection in D2 gastrectomy for locally advanced distal gastric cancer. METHODS: A retrospective cohort study was carried out. A total of 796 patients with locally advanced distal gastric cancer undergoing D2 gastrectomy at the Cancer Center of Guangzhou Medical University between 2002 and 2016 were enrolled. INCLUSION CRITERIA: locally advanced distal gastric adenocarcinoma confirmed by postoperative pathology; adenocarcinoma located at or invaded into lower 1/3 stomach; lymphadenectomy was D2 or D2+; negative resection margin confirmed by pathology; no distal metastasis was found; preoperative neoadjuvant chemotherapy was not administrated. Patients with undefined group of lymph nodes by postoperative pathology and those who were died perioperatively were excluded. Among 796 patients, 293 underwent No.14v dissection (No.14vD+ group) and the other 503 patients did not undergo No.14v dissection (No.14vD- group). The 5-year overall survival was compared between the two groups. Therapeutic index of No.14v lymph nodes was calculated according to the following formula: therapeutic index=metastatic rate of No.14 lymph nodes (%) × 5-year survival rate of patients with No.14 lymph node metastasis(%) × 100. Meanwhile, stratified analyses based on pathological TNM staging were performed. RESULTS: There were no significant differences in age, gender, tumor size, Borrmann type, Lauren classification, histological type, surgical procedure, and number of harvested lymph node between two groups (all P>0.05). However, compared to No.14vD- group, No.14vD+ group had more advanced T staging (χ² =14.771, P=0.005) and TNM staging (χ² =18.339, P=0.003), and higher ratio of receiving adjuvant chemotherapy (χ² =4.205, P=0.040). The median follow-up period was 47 months. The 5-year survival rate in No.14vD+ and No.14vD- groups was 57.4% and 46.8% respectively without statistically significant difference (P=0.313). After adjusting for confounding factors, Cox proportional hazards model showed that No.14v lymphadenectomy was not an independent prognostic factor(HR=0.802, 95%CI: 0.545-1.186, P=0.124). Stratified analyses revealed that in all TNM stages, 5-year survival rates were not significantly different between two groups (all P>0.05). However, No.14v lymphadenectomy showed a tendency of survival benefit when the tumor staging after advancing to III A stage(III A: P=0.103; III B: P=0.085; III C: P=0.060). Five-year survival rates of No.14vD+ and No.14vD- groups in stage III A were 54.9% and 45.2%, in III B stage were 39.8% and 29.5%, in III C stage were 27.5% and 16.2%, respectively. After combining III A, III B and III C, the No.14vD+ group had a higher 5-year survival rate than No.14vD- group (39.2% vs. 27.7%, P=0.006). The No.14v metastasis rate in No14v+ group was 12.6%(37/293), including 0%(0/46), 2.5%(1/40), 4.9%(2/41), 15.7%(8/51), 20.8%(11/53) and 24.2%(15/62) in stages I B, II A, II B, III A, III B and III C respectively. The metastasis rate of No.14v lymph node in stage III patients was 20.5%(34/166). The 5-year survival rate of these 34 stage III patients with No.14v metastasis was 21.1%. The therapeutic index of No.14v lymph node in stage III patients was 4.3, which was comparable with 3.9 of No.9 and 4.9 of No.11p, even higher than 2.6 of No.1. CONCLUSIONS: Although No.14v lymphadenectomy can not improve the overall survival of patients with locally advanced distal gastric cancer, but it may significantly improve survival in those with stage III cancer. The therapeutic index of No.14v lymph node is similar to No.2 station lymph node in patients with stage III distal gastric cancer. Therefore No.14v lymph node should be included in D2 dissection.