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Suppressive therapy of recurrent genital herpes is a challenge, and melatonin may be an alternative., Objective: To evaluate the action of melatonin, acyclovir, or the association of melatonin with acyclovir as a suppressive treatment in women with recurrent genital herpes., Design: The study was prospective, double-blind, and randomized, including 56 patients as follows: (a) The melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container ( n = 19); (b) The acyclovir group received 360 capsules of 400 mg acyclovir twice a day (one capsule during the day and another during the night) ( n = 15); (c) the melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container ( n = 22). The length of treatment was six months. The follow-up after treatment was six months. Patients were evaluated before, during, and after treatment through clinical visits, laboratory tests, and the application of four questionnaires (QSF-36, Beck, Epworth, VAS, and LANNS)., Results: No statistically significant difference was observed for the depression and sleepiness questionnaires. However, in the Lanns scale for pain, all groups decreased the mean and median values in time ( p = 0.001), without differentiation among the groups ( p = 0.188). The recurrence rates of genital herpes within 60 days after treatment were 15.8%, 33.3%, and 36.4% in the melatonin, acyclovir, and association of melatonin with acyclovir groups, respectively., Conclusion: Our data suggest that melatonin may be an option for the suppressive treatment of recurrent genital herpes.