Recurrent infection with herpes simplex virus is a common disease. Recently, alternative therapies have been introduced. Among those, low-intensity laser therapy mainly used for the acceleration of wound healing and in pain therapy has previously been shown to be of benefit in herpes zoster infections. In this study we evaluated the influence of low-intensity laser therapy (wavelength 690 nm, intensity: 80 mW per cm2, dose: 48 J per cm2) in 50 patients with recurrent perioral herpes simplex infection (at least once per month for more than 6 mo) in a randomized, double-blind placebo-controlled trial design. Patients in the laser group received daily irradiations for 2 wk, whereas patients in the placebo group were sham-irradiated. After completion of the laser/sham treatment, patients were asked to return to the Department of Dermatology, University of Vienna Medical School at the time of recurrence. All except two patients completed the study and were monitored for 52 wk. The median recurrence-free interval in the laser-treated group was 37.5 wk (range: 2-52 wk) and in the placebo group 3 wk (range: 1-20 wk). This difference was found to be statistically significant (p < 0.0001; Wilcoxon's Rank Sum Test). In conclusion, we demonstrated that a total of 10 irradiations with low-intensity laser therapy significantly lowers the incidence of local recurrence of herpes simplex infection. Since this athermic phototherapeutic modality represents a safe, noninvasive treatment, it might be considered as an alternative to established therapeutic regimens in this indication.