Objective To investigate the occurrence of sharp instrument injuries among healthcare workers in a comprehensive teaching hospital and explore the risk factors, so as to provide scientific basis for the prevention approaches. Methods A total of 1 180 healthcare workers with sharp instrument injuries between 2011 and 2014 were included in the study. Occupational hematogenous exposure monitoring and protecting system for health workers was established and optimized. The report and treatment process was standardized. Targeted monitoring system of sharp instrument injuries was developed. Sharp instrument injuries between 2011 and 2014 were systematically collected and analyzed. Results Between 2011 and 2014, there were 1 180 health workers who had sharp instrument injuries. Health workers had the highest rate of exposure to hepatitis B virus(41.06%), followed by syphilis (13.35%). Syringe needles (27.54%), suture needles (24.15%) and scalp needles (19.58%) were the instruments that caused most of the injuries. We constructed occupational exposure records for all those with sharp instrument injuries, and performed regular follow-up. No hematogenous infections were found because of sharp instrument injuries. Conclusions Sharp instrument injuries are common in healthcare institutions. It is important to establish and perfect the occupational exposure monitoring and protecting system, so as to reduce the risk of occupational exposure for health workers in hospitals.