Although recent reviews suggest few gender differences in smoking-cessation outcomes, it is important to establish whether gender differences exist in response to the brief interventions increasingly recommended as part of routine medical care. We used data from an efficacious primary care-based smoking intervention to examine gender differences in smoking characteristics, use of intervention components, self-reported quitting activities, and cessation outcomes among all smokers randomized to receive clinician advice and nurse-assisted intervention (n = 1,978, 58% female). Although female and male smokers differed on a number of sociodemographic and smoking-related characteristics, they were equally likely to participate in each step of the recommended intervention. Female and male smokers were also equally likely to report quit attempts and cessation at 3, 12, and 3 and 12 months (combined long-term cessation endpoint). Similarly, no gender difference in relapse at 12 months was seen. Women attempting to quit used a greater number and variety of smoking-cessation strategies, suggesting that, although outcomes were similar, the processes of cessation may vary by gender. Since this brief intervention in primary care was equally efficacious and acceptable to female and male smokers, broader implementation in medical settings of this population-based approach to reducing tobacco use is warranted. Indeed, widespread implementation of smoking-cessation programs in medical settings may particularly benefit women, who are more likely than men to have contacts with the medical care system.