Background: Postoperative infections significantly impact patient outcomes and healthcare costs in orthopedic trauma surgery. Accurate knowledge of the prevalence and microbiological characteristics of these infections is essential for enhancing treatment protocols and improving patient care. Methods: This cross-sectional study involved 200 patients who underwent orthopedic trauma surgery at a tertiary care center. We assessed the prevalence of different types of postoperative infections and characterized the microbiological profiles through standard culturing techniques and antibiotic susceptibility testing. Results: The study identified a varied prevalence of postoperative infections categorized specifically as Superficial Incisional Infection, Deep Incisional Infection, Organ/Space Infection, and Implant-Associated Infection, with respective occurrences of 5%, 14%, 7%, and 9%. The microbiological analysis revealed a dominance of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and MRSA. Notably, there was significant antibiotic resistance, particularly against methicillin, fluoroquinolones, and beta-lactam antibiotics, which are commonly used in prophylactic regimens. Statistical analysis showed a significant relationship between the type of surgery and the likelihood of developing an infection (p < 0.05). Conclusion: The findings underscore the need for enhanced infection control practices and tailored antibiotic prophylaxis in orthopedic trauma surgery. The prevalence and microbiological profile of postoperative infections call for rigorous microbiological surveillance and targeted therapy as integral components of postoperative care to reduce infection rates and address antibiotic resistance effectively.