The  standard laparoscopic cholecystectomy is  usually performed using a monopolar electrocautery for dissection and clips for occlusion of the cystic duct and cystic  artery. Some pitfalls are associated with the use of the monopolar cautery and clips, therefore other alternative techniques have been described. Ultrasonically activated  devices  have been used for dissection and cystic  duct ligation during  laparoscopic cholecystectomy (LC)  with encouraging results, however it does not gain widespread acceptance among  surgeons. The aim of the present  study was to compare the surgical outcome of LC performed  by the harmonic scalpel to that peiformed by the conventional diathermy and clips. Material and methods:  This prospective randomized comparative study included 30 patients (group A) in whom LC was conducted using the conventional method by clipping both the cystic duct and artery with dissection of gallbladder from liver bed by monopolar electrocautery (clips and cautery method = CCM), and 30 patients (group B) who were operated on using laparoscopic harmonic scalpel  (LHS) for closure and division  of cystic duct and artery and for dissection of gallbladder from liver bed. Our primary  end point was the biliary complications; however other intraoperative and postoperative parameters were included: bleeding, duration of operation, postoperative pain, and other complications. Results: Demographic data was similar in both groups. The operative duration was shorter in LHS than CCM  (56.3  min vs. 63.3 respectively, p < 0.01), with a significant less incidence of gallbladder peiforation (6.66% vs. 20%, p < 0.001).No postoperative bile leak was encountered in LHS, but it occurred in 3% of patients in CCM   No patient developed  post operative bleeding in both groups however the amount  of postoperative drainage was significantly less in LHS (29 vs. 47.7, p = 0.001). Most of patients  were discharged from hospital on 2nd postoperative day; however the delayed  discharge was statistically higher  in CCM  (16.6% vs. 6.66%, p < 0.01). Conclusion: LHS is a reliable, effective and safe tool in LC. It is a good alternative to standard monopolar electrocautery dissection with clipping of cystic duct and artery. It provides a shorter operative duration, less incidence of  gallbladder perforation, and  less hospital stay. Abbreviations: CCM= Clip and cautery method, LC= Laparoscopic cholecystectomy, LHS= laparoscopic harmonic scalpel, HFMC= high frequency monopolar cautery, BDI=  bile duct injury, CBC= complete blood picture, INR= international normalized  ratio, LFT= liver function test, UIS= ultrasonography.