Objective: To determine the safety and efficacy of ligasure vessel sealing system (LVSS) in controlling cystic artery in laparoscopic cholecystectomy: An initial experience on 50 patients at tertiary care hospital. Subjects and Methods: This descriptive cross-sectional study was done at Department of Surgery, Liaquat University of Medical Health Sciences, Jamshoro, during one year from April 2019 to March 2020. Patients aged 18 years or older, undergoing elective laparoscopic cholecystectomy for symptomatic gallstones, patients with a cystic artery diameter of less than or equal to 5mm were included. During laparoscopic cholecystectomy procedure the cystic artery in the Calot's triangle was identified. After creating space, the LVSS device was placed over the cystic artery and device was activated to seal the cystic artery. Once the cystic artery was sealed, the artery between the two sealed points has been divided. The most important outcome measure was the amount of bleeding that occurs during the procedure and complications such as bile duct injury, hepatic artery injury, or perforation can occur during laparoscopic cholecystectomy. The use of LVSS should result in minimal bleeding and without complications indicating that the cystic artery has been effectively sealed. All the data was collected via self-made study proforma and SPSS version 26 was used for analysis of data. Results: A total of 50 patients were included who had undergone laparoscopic cholecystectomy. The average age of the patients was 39.28+13.34 years, and the majority (80.0%) were female. Among the patients, 60.0% had multiple stones and 40.0% had a single stone. Based on anatomical position, the tract was straight in 44.0% of cases and curved in 38.0% of cases. In 16.0% of cases, the cystic artery arose from the right hepatic artery, and in one patient, the cystic artery was located behind the cystic duct. The surgery lasted for an average of 33.12+7.29 minutes, and there was an average blood loss of 13.44+3.7 ml. The mean hospital stay was 1.38+0.49 g/dl. There were no complications observed during or after the surgery. Conclusion: In conclusion, the Ligasure Vessel Sealing System (LVSS) observed to be an effective and safe method for controlling the cystic artery during laparoscopic cholecystectomy, with advantage of short operative time, no use of metallic clips, negligible blood loss, short hospital stay and no complications reported during or after the surgery.