Background: Cholecystectomy is one of the most commonly performed surgery overall. One of the most important steps in the operation of cholecystectomy whether open or laparoscopic, is the closure of cystic duct which if not done properly can lead to disastrous postoperative outcome. This study was conducted with an aim to do in vitro comparison of ultrasonic shear and standard titanium ligating clips in closure of cystic duct with respect to their ability to withstand the pressure generated inside the gall bladder by pneumatic tourniquet device.Methods: A total 148 patients underwent open or laparoscopic cholecystectomy Between August 2016 to October 2017 at Sir Sayajirao Gaekwad Hospital, Baroda, were eligible for this prospective randomized study. A total of 16 cases were excluded from the study and specimens from 132 patients were included in the study. The eligible patients were randomized into two groups using sealed envelopes. The two groups were as follows: A) ligating titanium clips, and B) ultrasonic shear. Independent assessors were assigned to obtain cystic duct bursting pressure.Results: A comparison of the mean cystic duct bursting pressure between both the groups indicated the superiority of ultrasonic shear group over ligating titanium clip group.Conclusions: The mean cystic duct bursting pressure was higher in the ultrasonic shears group than in ligating clips group, higher than the maximum cystic duct bursting pressure (195 mmHg). The ultrasonic shear provides safe alternative to standard titanium ligating clip for cystic duct closure.