Purpose: Several studies reported a difference in herpes zoster (HZ) incidence between males and females, but limitations in design and analysis impeded the assessment of gender as an independent risk factor for HZ. This study examines the independent etiologic association between gender and HZ. Methods: A total of 335,714 persons were observed prospectively during 2001. We registered gender and HZ occurrence, as well as other risk factors for HZ. We calculated overall crude and adjusted odds ratios (ORs) and stratified to age. Results: The HZ incidence in females was 3.9/1000 patients/year (95% confidence interval [CI], 3.6-4.2), and in males, 2.5/1000 patients/year (95% CI, 2.3-2.8), with a crude OR of 1.53 (95% CI, 1.36-1.74). After adjustment for potential confounders, the adjusted OR was 1.38 (95% CI, 1.22-1.56). The incidence was greater in females in the middle-aged (age, 25 to 64 years; OR range, 1.36 to 1.83) and youngest group (OR, 1.31; 95% CI, 0.90-1.89). Gender effect was inverse in young adults (age, 15 to 24 years; OR, 0.64; 95% CI, 0.41-1.03). Conclusion: Female gender is an independent risk factor for HZ in the 25- to 64-year-old age groups.