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The aim of this study was to investigate possible associations between (i) comorbid disease and (ii) perioperative risk factors and morbidity following radical surgery for gastric cancer.Consecutive patients (759) undergoing radical gastrectomy and D2 level lymph node dissection for gastric cancer were included. Clinical data concerning patient characteristics, operative methods, and complications were collected prospectively. Results: The morbidity rate for radical gastrectomy was 14.2% (108/759). The most significant comorbid risk factors for postoperative morbidity were heart disease [anticoagulant medication: OR = 1.5 (95% CI = 0.35-6.6, P = 0.53); history without medication: OR = 4.0 (95% CI = 1.1-14.6, P = 0.03); history with current medication: OR = 6.7 (95% CI = 1.5-29.9, P = 0.01)] and chronic liver disease [chronic hepatitis: OR = 2.4 (95% CI = 0.9-6.5, P = 0.07); liver cirrhosis class A: OR = 8.4 (95% CI = 2.8-25.3, P = 0.00); liver cirrhosis class B: OR = 9.38 (95% CI = 0.7-115.5, P = 0.08)]. The most significant perioperative risk factors for postoperative morbidity were high TNM stage and combined organ resection (P < 0.05), and there was no association between increased postoperative morbidity and well controlled hypertension, anticoagulant therapy, diabetes mellitus, pulmonary disease, tuberculosis, or thyroid disease (P > 0.05).Patients with heart disease or chronic liver disease are at a higher risk of morbidity following radical surgery for gastric cancer.