The primary aim of this study was to examine gender differences in perceived risks and benefits of smoking cessation and their relationship to pretreatment motivation and treatment outcome. No validated measures that comprehensively assess perceived risks and benefits associated with smoking cessation were available in the literature; consequently, we developed a self-report instrument [Perceived Risks and Benefits Questionnaire (PRBQ)] for this purpose. A sample of 573 treatment-seeking smokers (48% female) entering smoking cessation trials completed the PRBQ, and its association with treatment outcome was assessed in a subsample of 93 participants. Overall, the PRBQ demonstrated good psychometric properties. Females indicated greater likelihood ratings of perceived risks and benefits than males. For women and men, perceived benefits were positively associated with motivation, and perceived risks were negatively associated with motivation and treatment outcome. Women evidenced stronger associations between perceived risks and pretreatment motivation, and treatment outcome. Knowledge of perceived risks and benefits associated with smoking cessation is critical for public education campaigns and could inform intervention strategies designed to modify sex-specific beliefs associated with lowered behavioral intentions to quit smoking.