Aim: To compare the effectiveness of a single dose of preventive antibiotic with the use of empirical post-operative antibiotics in preventing Surgical Site Infection (SSI). Material and methods: The study group consisted of 100 patients, while the control group consisted of another 100 patients. The patients were evenly split into two groups: Group A, designated as the study group, and Group B, designated as the control group. The study group participants were given a single 1gm dose of cefotaxime injection either during the induction or 30 minutes before to making an incision in the skin. No more intravenous or oral antibiotics were administered to them. The second group of patients were administered cefotaxime 1gm I.V. BD injections for a duration of five days. If the patient was underweighting or obese, the dosage was modified based on their body weight. In the control group, patients who had laparoscopic cholecystectomy and were released within 2 to 3 days were prescribed Tab. cefixime 200mg BD for the same duration. Results: The majority of patients in both groups, namely 91% and 89%, did not have high fever after the operation. However, 9% of patients in the study group and 11% in the control group reported having a fever. The laboratory confirmed the predominant growth of Streptococcal, Staphylococal aureus, and E. coli in the surgical site of the control group. The participants or patients in this group received conventional antibiotic treatment for 3-4 days after the surgery. Out of the 7 patients, some showed the presence of these organisms in their pus or contaminated wound, albeit in smaller quantities. Out of the patients, several tested positives for infections, although this link was not statistically significant (p = 0.11).There were 5 patients in the pre-operative single dose antibiotic study group who had proven surgical site infections. In contrast, the control group had 7 patients with surgical site infections.Consequently, the rate of infection among the patients who got a single dosage of antibiotic before surgery was determined to be 7%. The incidence rate in patients was 9%, suggesting that the pre-operative antibiotic seemed to be more successful in preventing post-operative infection. However, this impact was not statistically significant (p = 0.22). Conclusion: We concluded that the single dose of antibiotic prophylaxis is enough for procedures that are classified as clean or clean contaminated