BACKGROUND: Reactivation of herpes simplex virus-1 (HSV-1) after facial resurfacing has led to severe outbreaks, delayed reepitheliazation, and scarring. Current recommendations regarding the dosing of antivirals used prophylactically are based mostly on anecdotal experience. No studies have addressed the question of when such antiviral prophylaxis should begin. OBJECTIVE: The purpose of this study was to compare the efficacy of valacyclovir used as an antiviral prophylaxis when started the morning before versus the morning of facial resurfacing procedures. METHODS: Eighty-four patients who presented for facial resurfacing were enrolled. Resurfacing was performed using laser (CO2, Er:YAG), chemical peeling, dermabrasion/dermasanding, or some combination of these techniques. Patients were randomly assigned to start valacyclovir 500 mg twice daily either the morning before or the morning of the procedure. Viral cultures were performed at baseline on all patients, at any sign of infection, and at the end of the 14-day treatment period. All patients were followed for 21 days postoperatively. RESULTS: Valacyclovir was 100% effective in the prevention of HSV reactivation in both regimens with no adverse effects reported. CONCLUSION: This study demonstrates the efficacy of valacyclovir as a preventive agent against HSV outbreaks following facial resurfacing whether started the day before or the day of surgery.