Background: Gold standard treatment of symptomatic cholelithiatis is laparoscopic cholicystectomy. No doubt, some minor biliary complication may occur by using monopolar hook,that is because of its thermal effect. In other way,use of ultrasonically activated harmonic scalpel,ie, (Ethicon Endo Surgery INC-Johnson & Johnson Medical SPA, Somerville, NJ) in laparoscopic cholecystectomies is increasing day bye day,for the purpose of dissecting gallbladder,vessels, and the cystic duct, because it reduces the risk of thermal injuries at operative field. Patients and Methods: This Comparative Study was conducted in surgical department of Ghulam Muhammad Mahar Medical Collage Hospital and Hira Medical Centre Sukkur during a period of last two years from july 2009 to june 2011. In duration of 2-years, we selected 92 patients, in which the, division and dissection of the cystic artery and duct is wholy soly done by Harmonic scalpal. We compared this group of patients with the data of a homogenous control group of patients, in which monopolar electrodiathermy and clips were used, in respect of average length of hospital stay, surgical time duration, and post operative complication. Results: Harmonic scalpel usage in surgery results shorter operative time but, there is no significant difference between operative and post operative complication in both group of patients. Conclusion: Harmonic scalpel has multiple function (coagulation, cutting, coaptation, and cavitation), so it is safe, effective and reliable instrument for gallblader surgery, specially in complicated cases. By using this instrument, you can save opertive time, anaesthesia time, operation theatre booking time, and operative as well as post operative complication.