Firearm injuries (FI) remain a significant cause of morbidity and mortality globally. Antibiotic use, supported by guideline recommendations for preventing post-injury infections in FI cases, encounters uncertainties regarding the selection of anti-microbial agents and associated outcomes. This study aimed to investigate the relationship between Injury Severity Scores (ISS) for FI cases presented to the emergency department. We empirically revised antimicrobial treatment protocols based on culture results and mortality rates. In the study, 164 firearm injury cases, admitted to the emergency department in 2022 and subsequently hospitalized in clinics and intensive care units (ICU), were evaluated. Cases included in the study were categorized into four groups based on ISS: mild, moderate, severe, and profound injury severity. The study compared the timing of hospital presentation following the injury, hospital length of stay, tissue or blood culture positivity, empirical treatment administered, antimicrobial revision based on culture results, need for ICU admission, mortality status, and ISS among the cases. Data were analyzed using IBM SPSS Statistics 22.0 (SPSS Inc., Chicago, IL). Variables in trauma patients were compared among various groups using Pearson Chi-Square tests. Binary logistic regression tests were performed to identify independent risk factors. A significance level of p<0.05 was considered statistically significant. The study included 164 patients, all of whom were male. The mean age was calculated as 28.9±4.51 years. The average hospital length of stay was 25.54±21.81 days. Eighty-three patients (50.6%) required intensive care. Tissue cultures were obtained from 79 patients (48%). Bacterial growth was observed in 45 of these 79 patients (57%). The appropriate empirical antibiotic treatment rate, assessed among patients who received empirical treatment followed by culture-based antibiotic sensitivity testing, was 48.9%. It was observed that empirical antibiotic regimens were appropriate in 80% of cases in the mild group and 16.7% in the profound severe group (p=0.005). Our study compared the relationship between hospitalization duration and ISS groups. It was observed that hospitalization duration was significantly shorter in the mild group compared to the other groups (p=0.003, p=0.000, p=0.000). It was also observed that the need for ICU admission was higher in groups with higher ISS, indicating a correlation between higher ISS and increased ICU requirements (p=0.000). In conclusion, for cases of firearm injuries, we believe empirical antimicrobial therapy should be initiated with narrow-spectrum agents such as beta-lactam + beta-lactamase inhibitor or third-generation cephalosporin + nitroimidazole in the mild group, considering the lack of Pseudomonal activity.