Rationale Recent studies describe an increasing prevalence of chronic obstructive pulmonary disease (COPD) and higher COPD exacerbation rates among women compared with men despite lower average cigarette use, which has raised the question of whether women are more susceptible to the effects of tobacco smoke. We examined associations between gender, cigarette smoking and COPD in a national dataset.Methods We used cross-sectional data for US respondents aged ≥40 years from the 2020 National Health Interview Survey (NHIS). Weighted multivariable logistic regressions assessed the relationship between gender and respondent-reported physician-diagnosed COPD, adjusting for tobacco use and sociodemographic covariates. Additional analyses were performed to determine if the relationship between cigarette smoking and COPD was modified by gender.Results Women had a higher COPD prevalence (7.8%) than men (6.5%) despite lower cigarette smoke exposure. Women were less likely to have ever smoked, and among respondents who had smoked, women had a lower average pack-year history compared with men. In multivariable regressions, female gender was associated with a higher risk of COPD (adjusted risk ratio 1.47, 95% CI 1.30 to 1.65) and the relative risk was similar for respondents both with and without a history of smoking. Moreover, there was no significant interaction between gender and smoking status or gender and pack-year exposure relating to COPD prevalence.Conclusions Among adults aged ≥40 years, women had a roughly 50% greater risk of COPD than men. Higher susceptibility to cigarette smoking in women did not explain the difference.