4562 Background: A few studies reported the association between helicobacter pylori (HP) infection and better overall survival (OS) in resected gastric cancer patients (pts). Methods: We investigated the HP infection status and its association with clinicopathologic characteristics in 210 locally advanced gastric cancer patients (stage IB: 18, II: 61, IIIA: 62, IIIB: 31, IV: 38) who underwent adjuvant chemotherapy (CTX) after curative resection (≥D2 dissection). HP infection status in hematoxlin and eosin stained peritumoral tissue was graded according to the updated Sydney System and categorized as HP(-) (normal or mild infection) and HP(+) (moderate or marked infection) (Am J Surg Pathol 20:1161, 1996). Twenty-two pts received 5-FU, doxorubicin (DOX) CTX (5- FU 500 mg/m2 weekly for 36 wks, DOX 40 mg/m2 q 3 weeks x 12) with or without OK432, while 188 pts underwent 5-FU, mitomycin-C (MMC), and polysaccharide-K (PSK) CTX (5-FU 500 mg/m2 weekly for 24 wks, MMC 8 mg/m2 q 6 wks x 4, PSK 3 g/day for 16 wks) (Br J Cancer 84:186, 2001, Hepatogastroenterol 54:290, 2007). Results: The median follow-up duration of survivors was 125 (107–155) months. HP (-) was significantly correlated with Bormann type IV, larger tumor size (>5.5cm),and stage IIIB. In univariate analysis, patients with HP(-) (104 pts) demonstrated significantly poor 10-year OS compared with those with HP (+) (106 pts) (15.9% vs. 87.7%, p<0.0001). HP(-) was associated with poor outcome in all stages except stage IB (p=0.075). In multivariate analysis, HP(-) was the most significant independent prognostic factor of poor OS (hazard ratio 9.646, 95% CI 5.407–17.206, p<0.0001) followed by advanced stage (p=0.032), Bormann type IV (p=0.037) and old age (p=0.015). Conclusions: HP infection status seems to have strong prognostic significance in locally advanced gastric cancer. HP (-) pts may need intensified adjuvant treatment and careful follow-up. No significant financial relationships to disclose.