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Objectives: To assess the dissection of gallbladder by ultrasonic harmonic scalpel in comparison to electrocautery in laparoscopic cholecystectomy. Study Design: A randomized control trial Study Setting and Duration: Department of Surgery Ward-02 Jinnah Postgraduate Medical Centre, Karachi between June 2018 and February 2019. Methodology: A total of 110 patients diagnosed with cholelithiasis were included in the study. The participants were randomly allocated into two groups i.e., harmonic scalpel group and electrocautery group. Patients were followed postoperatively in the ward and the outcome was measured at the end of two days after surgery. Results: The average age of the patients was 44.56 ± 12.19 years. Out of 110 patients, 30 (27.3%) were male and 80 (72.7%) were female. It was found that the mean operative time (44.4 ± 3.64 min vs. 53.31 ± 8.09 min; p=0.0005), blood loss (10.27 ± 8.35ml vs. 4.00 ± 3.65ml; p=0.0005), post-operative pain (6.87 ± 1.04 vs. 4.29 ± 1.01 p=0.0005), and hospital stay (31.09 ± 10.58 vs. 24.11 ± 0.81; p=0.0005) were significantly lower in harmonic scalpel group than the electrocautery group. Conclusion: Dissection of gall bladder with harmonic scalpel is safe and easy method and superior then electrocautery and can routinely be used if available. Keywords: Laparoscopic cholecystectomy, Harmonic scalpel, Electrocautery