Background: This study evaluates the effectiveness and safety of the Harmonic scalpel for dissection of the gallbladder and its efficacy in the closure of the cystic artery and duct. This study, albeit at a preliminary stage, aims to demonstrate that the ultrasonically activated scalpel is safe instrument that, similarly to the standard titanium clips, is effective for correct and complete division & closure of the cystic duct & artery in laparoscopic cholecystectomy. Use of a single instrument during the whole procedure averts or decreases the risk of organ injuries related to thermal damage & alleviate the need for changing instruments frequently. Materials & methods: All cases of having gall bladder stones detected preoperatively by ultrasound & symptomatic gall stone disease were divided equally into 2 groups and planned for harmonic scalpel assisted clipless laparoscopic cholecystectomy & conventional laparoscopic cholecystectomy, were included in this study. Patients with Mirizzi syndrome, Age < 18 and >70 years, Impaired liver function tests, Concomitant common bile duct calculi, Chronic liver disease/cirrhosis, Suspected GB carcinoma, Pregnant women and patients in whom subtotal cholecystectomy was done were excluded from this study. A prospective study was carried out for 76 patients for 1.5 year from December 2022 to June 2024 by single surgeon and his team. Half of the patients were subjected to harmonic scalpel assisted laparoscopic cholecystectomy without application of the titanium clips, using 3 port technique after documentation of GB calculi using ultrasonography for diagnosis other half were subjected to conventional method of laparoscopic cholecystectomy. All patients were followed up for 1 month for SSI. All the results were recorded in Microsoft excel sheet and were subjected to statistical analysis using SPSS software. Results: We performed total 76 laparoscopic cholecystectomies from December 2022 to June 2024. Out of them, 78.94% were female and 21.05% were males in both the groups. In the Conventional Cautery group, the majority of subjects (36.84%) are in the 36-45 years category, while the next highest distribution is in the 46-55 years group (18.42%). Similarly, in the Harmonic Scalpel group, the majority of subjects (31.57%) are also in the 36-45 years category, followed by a significant portion (26.31%) in the 26-35 years category. The mean age in the Conventional Cautery group is 46.57 ± 14.00 years, while the Harmonic Scalpel group has a lower mean age of 40.73 ± 13.36 years. We found that the Intraoperative time for clipless Laparoscopic Cholecystectomy using the Harmonic scalpel is far lower than the conventional method of using cautery, Easy dissection of calot’s triangle. Harmonic scalpel can seal & cut the cystic duct and artery without using thermal energy with no lateral spread & therefore saving the time to apply titanium clips & preventing inadvertent damage. Easy dissection of gall bladder from the fossa and dissection of adhesions over it. There is no smoke while using harmonic scalpel therefore no difficulty in vision. There was no GB perforation & CBD injury. None of the patients converted to open & none of them had bile leak or postop SSI. Conclusion: Harmonic scalpel assisted laparoscopic cholecystectomy is better in all aspects & can be routinely used without any intra & post operative complications using standard operative guidelines. Laparoscopic cholecystectomy without application of titanium clips did not produce any harm to patient with the mean operative time was significantly shorter, with shorter hospital stay. It was observed that it is easy to dissect gall bladder from fossa, dissection of adhesions from gall bladder with the help of Harmonic scalpel. There was reduced intraoperative time & Anaesthesia time therefore mild postoperative pain and analgesia requirement in patients.