Objective To explore the effect, cost and safety of pressure steam sterilization, low temperature plasma sterilization and ethylene oxide sterilization on laparoscopic device. Methods A total of 90 sets of laparoscopic device in a tertiary first-class hospital from November to December 2020 were selected. According to random number table method, laparoscopes after cleaning, drying and packaging were respectively sterilized by the above three sterilization methods, with 30 sets in each group. Sterilization effect was monitored, time and economic cost of three sterilization methods were analyzed, sterilization safety was compared. Results Qualified rates of physical, chemical and biological monitoring of sterilization effect of three groups of laparoscopes were all 100.00%, quality of optical imaging were all 100.00%. The average sterilization time of pressure steam sterilization, hydrogen peroxide low temperature plasma sterilization and ethylene oxide sterilization were 3, 21.7 and 320 minutes respectively; cost of sterilization and maintenance of each set of laparoscope were 1.32, 23.74 and 100.46 Yuan/set respectively; cost of consumables required for sterilization of each set of laparoscope were 15.60, 116.67 and 106.67 Yuan respectively; the required human cost were 1.55, 11.17 and 164.96 Yuan/set respectively. The average overall cost for sterilization of each set of laparoscope by three sterilization methods were 18.47, 151.58 and 372.09 Yuan/set respectively. There was no disinfectant residue in pressure steam sterilization method, and there was no adverse reaction among health care workers; there was disinfectant residues in hydrogen peroxide low temperature plasma and ethylene oxide sterilization, which had irritation to the eyes, respiratory tract and skin of health care workers. Conclusion Compared with the other two methods, pressure steam sterilization has obvious advantages in time, cost and safety, it is suitable for heat-resistant and moisture-resistant laparoscopic device sterilization.