Objective To analyze main causes of occupational exposure of medical staff and to propose preventive measures for decreasing the occurrence of occupational exposure. Methods The data of 250 reported cases of occupational exposure in Ruijin Hospital from January 2012 to December 2013 were collected and main causes of occupational exposure were analyzed. Preventive treatments were conducted according to their actual situations and tracking survey and follow-up analysis were performed. Results The results of analysis of 250 reported cases of occupational exposure showed that top two exposure rates were observed among nurses (58.80%) and doctors (32.00%). Needle stick injuries (NSIs) were the most common cause (94.00%), which occurred frequently during needlewithdrawing and suturing. Unknown causes, negative causes or causes confirmed to be negative afterwards, and hepatitis B virus accounted for 34.00%, 32.40% and 23.20% respectively. Most cases underwent local treatments and disinfection properly and were reported immediately. Relevant preventive measures were taken and no blood borne infections were found by detections conducted afterwards. Conclusion Analysis of causes of occupational exposure of medical staff facilitates identifying the key target group of occupational safety education, taking relevant preventive measures, and decreasing the risk of occupational exposure.