<p class="abstract"><strong>Background:</strong> The association of cholecystectomy with alterations in lipid profile is well documented. Objectives of this study were to determine the effect of cholecystectomy on lipid profile of cholelithiasis patients.</p><p class="abstract"><strong>Methods:</strong> This cross-sectional observational study was done on 170 patients admitted in general surgery department of Naz Memorial Hospital, Karachi from July 2018 to June 2019. Symptomatic cholelithaisis patients between 18 to 60 years, elective cholecystectomy was included while patients previously on lipid lowering agents, diagnosed renal failure, nephrotic syndrome, cardiac failure, pregnant mothers, hypothyroidism, pancreatitis and obstructive jaundice were excluded. For data analysis, SPSS was used. Wilcoxon signed ranked test was used to compare mean values of pre and post-operative lipid profiles after cholecystectomy keeping p value of &lt;0.05 as significant.  </p><p class="abstract"><strong>Results:</strong> 60% of patients were females with majority, 31% patients between 31-40 years while least, i.e. 11% were between 61-70 years. The mean pre-operative and post-operative difference of 52±7.32 mg/dl was seen in total cholesterol levels (p&lt;0.001). The mean difference in high density lipoprotein (HDL) between pre and post-operative was of 13±0.36 mg/dl (p&lt;0.001). The mean difference in low density lipoprotein (LDL) between pre- and post-operative was 61±10.45 mg/dl (p&lt;0.001). The mean difference in triglycerides levels between pre- and post-operative was 46±25.49 mg/dl (p&lt;0.001).</p><p class="abstract"><strong>Conclusions:</strong> Cholecystectomy in gall stone disease patients elicited favorable response in significantly lowering levels of total serum cholesterol, LDL and triglycerides while substantially increasing levels of HDL cholesterol.</p><p> </p>