Background: Radiation therapy has improved survival in gastric cancer in some randomized trials. However, post-operative fields have been difficult tolerate, and completion rates have been low. Preoperative therapy may afford the opportunity to radical therapy, and potentially improve the resectability in advanced patients. Methods: Patients with Siewert II/III GE junction or gastric cancer treated at Massachusetts General Hospital were evaluated with Institutional Review Board approval. Clinical parameters and prognostic factors including gender, age, clinical stage, pathological stage, radiation parameters, concurrent chemotherapy, non-radiation chemotherapy, toxicity and survival were included in the analysis. Results: From Jul 2005 to Jan 2017, we enrolled 88 patients had chemoradiotherapy (CRT) and surgery, 48 preoperative and 40 postoperative CRT patients. In the preoperative group, 16.7% (8/48) had nodes outside a standard D2 dissection range, and the pathologic complete regression (pCR) rate was 18.8% (9/48). Median preoperative and postoperative radiation dose was 50.4 Gy and 45 Gy. Two-drug regimen was the most commonly used preoperative concurrent chemotherapy: 60.5% and single drug was the most commonly used postoperative concurrent chemotherapy: 97.5%. Except concurrent chemotherapy, 25 preoperative CRT patients received induction FOLFOX (median 8 cycles); 9 postoperative CRT patients also received 5-FU and 23 received FOLFOX (or EOX) chemotherapy. The estimated 3-year relapse-free survival (RFS) and overall survival (OS) in the preoperative and postoperative group was 51% vs. 34.3% (p = 0.286), and 71.2% vs. 45.9% (p = 0.179), respectively. In preoperative CRT group, there was more hematological toxicity but less gastrointestinal toxicity than postoperative CRT group, more distant metastasis but less peritoneal recurrence rate. Conclusions: Compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy option has the trend of better tolerance, higher RFS and OS in patients with local advanced gastric cancer. Different chemoradiotherapy strategy may lead to different recurrence patterns.