Objective The aim of the study was to evaluate the role of postoperative sequential chemotherapy and radiotherapy in patients with locally advanced gastric cancer. Methods From January 2003 to December 2010, 146 gastric cancer patients at our institution (Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) received postoperative sequential chemotherapy and radiotherapy after radical surgery. Radiotherapy was administered as a dose of 4500 cGy in 25 fractions. For patients with positive margins, the dose was raised to 5040 cGy in 28 fractions. Three cycles of mFOLFOX or PF (cisplatin, 5-fluorouracil) chemotherapy regimen were applied before and after radiotherapy. Three- and 5-year survival rates were analyzed; any adverse effects with respect to hematology, hepatic and renal function, or the gastrointestinal tract that occurred during the treatment were evaluated. Results This cohort consisted of non-metastatic patients: 104 men and 42 women with a median age of 51.0 years. The full course of sequential chemotherapy and radiotherapy (4500–5040 cGy) was completed by 129 patients (88.4%). Seventeen regional relapses (9.8%) and 46 distant relapses (23.8%) were recorded. Fifty patients (34.2%) died during follow-up. The 3- and 5-year overall survival rates (OS) were 60% and 54%, and disease-free survival rates (DFS) were 53% and 47%, respectively. There were no significant differences in survival rate with respect to age, sex, histopathology, N stage, site of the tumor, or margin status. Multivariate analysis showed that only the depth of tumor invasion (T stage) was an independent prognostic factor for OS (P = 0.009) and DFS (P = 0.006). The rates of grades 3 and 4 neutropenia and vomiting were 9.6% and 3.4%, respectively, during the treatment. Conclusion Postoperative sequential chemotherapy with an mFOLFOX or PF regimen and radiotherapy were found to be an effective means of treating advanced gastric cancer patients with T3–T4 disease. The adverse effects of this treatment were tolerable.