Background: Prognosis for locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, remains unsatisfactory, even with D2 gastrectomy followed by adjuvant chemotherapy. Neoadjuvant chemotherapy is a promising approach, and combination chemotherapy with Xeloda and oxaliplatin (G-XELOX) is recognized as a potentially promising regimen for gastric cancer. However, the use of neoadjuvant chemotherapy consisting of G-XELOX for locally advanced gastric cancer has not been reported. The aim of this study was to evaluate the incidence of dose limiting toxicities (DLTs) during the neoadjuvant chemotherapy and to determine the maximum tolerated dose (MTD) and recommended dose of preoperative chemotherapy combined with oxaliplatin with a fixed Xeloda dose for locally advanced gastric cancer. Methods: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1, as well as Xeloda (2000 mg/m²/day, b.i.d.) for 14 days, repeatedly every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant S-1 (80 mg/m²/day, b.i.d.) for one year. A decrease of oxaliplatin dose was planned (starting at level 1, 130 mg/m²). Results: Six patients (5 male, 1 female) with a median age of 72 (range 68-79) were enrolled. MTD was not reached at level 1. Oxaliplatin 130 mg/m² in combination with Xeloda 2000 mg/m²/day, b.i.d. could be administered with acceptable toxicity. No treatment-related death was observed. Most frequent drug-related AEs during the neoadjuvant chemotherapy period were G1 anemia, G1/2 thrombocytopenia and G1 peripheral neuropathy. One patient refused surgical resection, therefore five received resection with curative intent. Of the five patients, all achieved a pathological downstaging after neoadjuvant G-XELOX therapy. The incidence of operative morbidity was tolerable. Conclusions: Neoadjuvant chemotherapy with G-XELOX regimen was feasible by patients with locally advanced gastric cancer. Clinical trial information: UMIN000015950.