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Objectives: To compare the mean operative time in subtotal thyroidectomy withharmonic scalpel and conventional vessel ligation method. Study Design: Randomized controltrial. Setting: Surgical unit of Bakhtawar Amin Medical and Dental College Multan. Period: April2015 to April 2016 for one year. Methodology: A total number of 92 cases were selected forthis study and these were randomly divided into two equal groups by lottery method (GroupA= operated with harmonic scalpel, Group B= operated with conventional vessel ligationmethod) each containing 46 patients. The sample size was calculated with the help of the WHOSample Size Calculator. (WHO sample size determination software version of KC Lun and PeterChiam). Sample Size, n= 92 (46 in each group). Expected mean operative time with harmonicscalpel method (44.9 ± 8.3 minutes) compared with the Conventional ligation method (69.5 ±10.7 minutes; P < .001). Data was analyzed with the use of SPSS version 23. The frequencyand percentage were calculated for qualitative variables like gender. Quantitative variables likeage and operative time were presented as mean and standard deviation. T test was appliedto compare the mean operative time between two groups. Results: A total number of 100%(n=92) patients were included in this study. Gender distribution showed that there were moremales i.e 52.2% (n=48) and 47.8% (n=44) were females. The mean age of patients was 42.75+ 14.33 years. Recorded mean duration of operation time was 47.69 + 6.51 minutes for groupA compared to the mean duration of operation of 71.61 + 7.32 minutes. This time differencewas statistically significant with a p-value of < 0.001. Conclusion: Subtotal thyroidectomy withharmonic scalpel leads to a significantly reduced mean operative time compared to conventionalvessel ligation technique and should be opted routinely for this surgical procedure.