BACKGROUND: A number of studies have reported on the association between smoking and meningioma risk, with inconsistent findings. We examined the effect of gender on the association between cigarette smoking and risk of intracranial meningioma in a large population-based, case-control study. METHODS: The data include 1,433 intracranial meningioma cases aged 29 to 79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Texas counties between May 1, 2006 and April 28, 2011 as well as 1,349 controls that were frequency matched on age, sex, and geography. The data are analyzed separately and in a meta-analysis with six previously reported studies. RESULTS: Female cases who reported having ever smoked were at significantly decreased risk of intracranial meningioma (OR, 0.8; 95% CI, 0.7-0.9) in contrast to male cases who were at increased risk (OR, 1.3; 95% CI, 1.0-1.7). Similar findings were noted for current and past smokers. Smoking-induced risk for females did not vary by menopausal status. For males, increased duration of use (P = 0.04) as well as increasing number of pack-years (P = 0.02) was associated with elevated risk. A meta-analysis including 2,614 cases and 1,179,686 controls resulted in an OR for ever smoking of 0.82 (95% CI, 0.68-0.98) for women and 1.39 (95% CI, 1.08-1.79) for men. CONCLUSION: The association of cigarette smoking and meningioma case status varies significantly by gender with women at reduced risk and men at greater risk. IMPACT: Whether the observed differences are associated with a hormonal etiology will require additional investigation.