ObjectiveThe extent of regional lymphadenectomy for proximal gastric cancer (PGC) has remained a controversy and a matter of considerable debate for a long time. We retrospectively analyzed the clinicopathological features to investigate the predictive factors for No. 5 and/or No. 6 lymph node metastases (LNMs) and evaluate the feasibility of performing proximal gastrectomy (PG) with preservation of No. 5 and/or No. 6 lymph nodes for these patients. MethodPatients who had undergone total gastrectomy plus D2 lymphadenectomy in the Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, from January 2008 to December 2017 were retrospectively collected and analyzed. ResultsAmong the 395 eligible patients in our study, 34 patients (8.61%) had No. 5 and No. 6 LNM. The degree of differentiation, Borrmann classification, vascular or perineural invasion, tumor diameter, depth of invasion, and other perigastric LNM were associated with No. 5 and/or No. 6 LNM. Multivariate analyses showed that tumor diameter >= 4 cm, No. 4 LNM positive, and No. 7, No. 8, No. 9 LNM positive were independent risk factors of No. 5 and/or No. 6 LNM. No. 5 and/or No. 6 LNM was not observed in the 105 patients who were staged from T1 to T3 and were found to be without independent risk factors. ConclusionThe metastatic rate of No. 5 and/or No. 6 lymph node of the proximal gastric adenocarcinoma was closely associated with the diameter of the tumor and other perigastric LNMs. It is feasible to preserve No. 5 and No. 6 lymph nodes with PG for the T1-T3 patients with lower risk of No. 5 and/or No. 6 LNM.