Objective To investigate the risk factors of upper gastrointestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs).Methods A total of 1032 patients which used NSAIDs was selected.Patients were divided into two groups based on the condition of dyspepsia,peptic ulcer or upper gastrointestinal bleeding:the adverse drug reaction group (331 cases) and the control group (701 cases).Data of two groups on clinical presentation,laboratory test,medication and treatment were analyzed.Risk factors for the adverse drug reaction were identified by multivariable Logistic regression.Results The two groups had significant difference in age ＞ 65 years old,Helicobacter pylori (Hp) infection,ulcer history,drug overdose,combination with glucocorticoid,addicted to tobacco and alcohol history,non-specific inhibitor of cyclooxygenase(COX)-2,combination with anticoagulant,concomitant chronic cardiopulmonary disease (P ＜ 0.05).Logistic regression analysis by backward elimination method revealed that following variables retained,such as combination with glucocorticoid (OR =3.104,95％ CI 1.936-4.695),Hp infection (OR =2.768,95％ CI 2.047-3.742),drug overdose (OR =2.411,95％ CI 1.683-3.453),ulcer history (OR =1.781,95％ CI 1.278-2.480),age ＞ 65 years old (OR =1.659,95％ CI 1.237-2.225),non-specific inhibitor of COX-2 (OR =1.470,95％ CI 1.103-2.133),addicted to tobacco and alcohol history (OR =1.459,95％ CI 1.032-2.064),concomitant chronic cardiopulmonary disease (OR =1.357,95％ CI 1.008-2.143),P＜0.05.Conclusion Combination with glucocorticoid,Hp infection,drug overdose,ulcer history,age ＞ 65 years old,non-specific inhibitor of COX-2,addicted to tobacco and alcohol history,concomitant chronic cardiopulmonary disease are risk factors of upper gastrointestinal injury induced bv NSAIDs.