Surgical site infection continues to be one of most common postoperative health care associated infections worldwide. SSIs are associated with significant morbidity and complications in the patient. Identifying an appropriate and effective modality of administration of antibiotics is need of the hour to minimize the SSIs. A prospective study was done among 100 patients who underwent elective and emergency surgeries in the department of General Surgery between October 2019 and June 2021 were included in the study. The patients were divided into 2 groups to receive cefotaxime either as intraincisional infiltration or intravenous route. The proportion of patients with signs of wound infection such as redness/warmth was significantly less with intraincisional infiltration than intravenous route (8% vs 26%). Presence of seroma was also significantly less with intraincisional infiltration (32% vs 51%). Thus, it is evident that intraincisional infiltration is more effective in preventing SSI than intravenous route.