AIM: To analyze the prognostic impact of lymphade- nectomy extent in advanced gastric cancer located in the cardia and fundus. METHODS: Two hundred and thirty-six patients with advanced gastric cancer located in the cardia and fundus who underwent D2 curative resection were analyzed retrospectively. Relationships between the numbers of lymph nodes (iNs) dissected and survival was analyzed among different clinical stage subgroups. RESULTS: The 5-year overall survival rate of the entire cohort was 37.5%. Multivariate prognostic variables were total LNs dissected (P<0.0001; or number of negative LNs examined, P<0.0001), number of positive INs (P < 0.0001), T category (P < 0.0001) and tumor size (P=0.015). The greatest survival differences were observed at cutoff values of 20 INs resected for stage II (P = 0.0136), 25 for stage III (P < 0.0001), 30 for stage IV (P = 0.0002), and 15 for all patients (P = 0.0024). Based on the statistically assumed linearity as best fit, linear regression showed a significant survival enhancement based on increasing negative INs for patients of stages III (P = 0.013) and IV (P = 0.035). CONCLUSION: To improve the long-term survival of patients with advanced gastric cancer located in the cardia and fundus, removing at least 20 INs for stage II, 25 INs for stage III, and 30 INs for stage 1V patients during D2 radical dissection is recommended.