Background: Surgical site infections (SSIs) present a formidable challenge in contemporary healthcare, impacting patient well-being and contributing to escalating healthcare costs. The judicious utilization of antimicrobial agents is paramount in effectively combating SSIs. This study, conducted at a Tertiary Care Teaching Hospital in Kerala, seeks to unravel the intricate patterns of antimicrobial agent usage within the General Surgery Department over 10 months. Aims and Objectives: The primary aim is to thoroughly examine antimicrobial agent patterns within the General Surgery Department, focusing specifically on patients undergoing surgical procedures. The study aims to assess the appropriateness of antimicrobial agent usage, encompassing the choice for prophylactic purposes, timing of pre-operative dosing, the occurrence of intraoperative dosing, and the selection appropriateness for post-operative prophylaxis. Materials and Methods: Crafted for robust analysis, the study included 150 cases, implementing specific inclusion and exclusion criteria to ensure data quality. The emphasis was placed on patients undergoing surgical procedures, focusing on prophylactic antimicrobial use. Data collection involved meticulously evaluating appropriateness across critical parameters, including the choice of prophylactic antimicrobial agent, pre-operative dosing timing, intraoperative dosing, and selection appropriateness for post-operative prophylaxis. Results: Analysis of 150 cases provided valuable insights into the age and gender distribution, predominantly within the 41–60 age groups. Prevalent surgical procedures, such as hernia and appendicitis, underscored the necessity for tailored antimicrobial protocols. Cephalosporins emerged as the dominant class, raising concerns about potential overuse and resistance. Pre-exposure prophylactic antibiotics, predominantly cephalosporins, were administered in 88 cases. Post-exposure prophylaxis mirrored this trend, necessitating a critical evaluation of antibiotic selection and duration. Detailed analysis of cephalosporin pre- and post-exposure prophylaxis identified prevalent choices such as Cefotaxime and Cefoperazone + Sulbactam, emphasizing the importance of scrutinizing cephalosporin selection. Conclusion: This study furnishes valuable insights into the appropriateness of antimicrobial agent usage for preventing SSIs, serving as a model for analogous healthcare settings. It underscores the significance of local antibiotic stewardship, guideline adherence, and the ongoing commitment to optimizing prophylactic antimicrobial usage for ensuring patient safety and advancing healthcare quality amidst evolving challenges.