BACKGROUND Cutaneous laser resurfacing is a well-accepted modality, with excellent clinical outcomes and low morbidity rates, for the treatment of a variety of epidermal and dermal lesions. The use of antibiotic prophylaxis continues to be an area of controversy, with laser practitioners divided in their approach. OBJECTIVE To identify the rate of postoperative bacterial infection following full-face carbon dioxide (CO2) laser resurfacing with and without antibiotic prophylaxis. METHODS A retrospective chart review of 133 consecutive patients following full-face CO2 laser resurfacing was performed. The rate, severity, duration, and subsequent treatment of bacterial infections observed in four treatment categories were recorded: (1) no antibiotic prophylaxis; (2) intraoperative single-dose intravenous cephalexin (1 g); (3) postoperative oral azithromycin (1.5 g over 5 days); (4) intraoperative IV cephalexin (1 g) and postoperative oral azithromycin (1.5 g). RESULTS A significantly higher rate of infection occurred in patients receiving combination intraoperative and/or postoperative antibiotic prophylaxis. The most frequently cultured organisms included Enterobacter and Pseudomonas species. CONCLUSIONS The rate of postoperative bacterial infections after full-face CO2 laser resurfacing in this retrospective study was not significantly reduced with the use of prophylactic antibiotics.