INTRODUCTION: Surgical site infections (SSI) complicate at least 5% of hand trauma operations; however, the efficacy of prophylactic antibiotics remains unclear. Unlike previous meta-analyses, this network meta-analysis (NMA) provides a definitive summary of all currently available data across multiple antibiotic classes, allowing indirect comparisons to provide a robust understanding of relative antibiotic effectiveness. METHODS: A systematic literature search was performed across EMBASE, MEDLINE, CINAHL, and CENTRAL, supplemented by Google Scholar and clinical trial registries. Prospective comparative studies comparing antibiotics versus placebo/no antibiotics in patients undergoing surgery for hand and wrist trauma were included. Data on SSI rates were extracted and analysed using network meta-analysis with frequentist random-effects models. RESULTS: Some 4499 articles were screened, with 13 randomized controlled trials (RCT) and 2 non-randomized studies involving 3898 participants included in the analysis. The pooled SSI prevalence was 3.6%. Our NMA indicated that prophylactic antibiotics did not significantly reduce SSI risk compared to placebo: the highest-ranking treatment (mixed antibiotic regimen) demonstrating a relative risk of 0.29 (95% c.i. 0.04, 2.13). Subgroup analyses revealed no significant differences based on injury type or location of surgery. CONCLUSION: There was insufficient evidence to support routine prophylactic antibiotic use in hand trauma surgery. Low event rates, wide confidence intervals, and moderate-to-high risk of bias in most included studies limit the certainty of this conclusion: the evidence remains inconclusive. Future high-quality RCTs are warranted to evaluate the benefit of antibiotic prophylaxis in hand trauma surgery.