AIM: To study the risk factors for morbidity and mortality following total gastrectomy. rnMETHODS: We retrospectively reviewed the records of 125 consecutive patients who underwent total gastrectomy for gastric cancer at the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2003 and March 2008. rnRESULTS: The overall morbidity rate was 20.8% (27 patients) and the mortality rate was 3.2% (4 patients). Morbidity rates were higher in patients aged over 60 [odds ratio (OR) 4.23 (95% confidence interval (CI) 1.09 to 12.05)3, with preoperative comorbidity [with vs without, OR 1.25 (95% CI 1.13 to 8.12)], when the combined resection was performed [combined resection vs total gastrectomy only, OR 2.67 (95% CI 1.58 to 5.06)]. CONCLUSION: Age, preoperative comorbidity and combined resection were independently associated with the rate of morbidity after total gastrectomy for gastric cancer.