Objective: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Methods: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. Conclusions: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.