Valacyclovir given in a 5-day regimen of 500 mg twice per day is effective as short-term treatment of episodes of recurrent genital herpes. This study compared the efficacy of a shorter, 3-day course (for 402 patients) with that of a 5-day course (for 398 patients) of valacyclovir for persons with frequent recurrence of symptoms. No significant differences were detected between the 2 dosing schedules for any of the end points measured. Median times to lesion healing, of pain duration, and of episode length for the 5-day versus 3-day treatment were 4.7 versus 4.4 days, 2.5 days versus 2.9 days, and 4.4 days versus 4.3 days, respectively. The proportions of patients with aborted lesions were 26.6% and 25.4% in the 5-day and 3-day groups, respectively. A 3-day course of 500 mg of valacyclovir administered twice daily as episodic treatment of recurrent genital herpes is equivalent to a 5-day course with regard to key markers of efficacy.