While international burn injury guidelines discourage prophylactic antibiotics on admission, current surgery guidelines focusing on antimicrobial prophylaxis place thermal injury under a general plastics procedure umbrella, and require significant evidential extrapolation. The purpose of this study was to determine if withholding systemic antibiotics in patients with <20% total body surface area (TBSA) burns without invasive wound infections and undergo wound excision is non-inferior to patients that receive preoperative antibiotics. Success was defined as lack of graft loss, bacteremia, or surgical site infection. One-thousand and eighty-three patients were screened and 100 patients undergoing 133 operations remained after exclusions. Seventy-four percent were male. Median age and %TBSA was 41 years (30, 55) and 5 (1.5, 8.3), respectively. We found no differences in demographics between patients that did and did not receive preoperative antibiotics. The success rates were 81.7% and 84.3%, respectively. There was one clinically significant bacteremia in each group. Withholding preoperative antibiotics was non-inferior with a percent difference of 2.6 (95% CI; -10.4, 15.6). Patients that did not receive antibiotics were no more likely to incur infection-related complications. In patients with <20% TBSA burns and without active wound infections, withholding preoperative systemic antibiotics will preserve unneeded antimicrobial exposure without increasing risk of infection-related complications. Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.