Abstract: Rationale: Understanding the health risks associated with extreme weather events is needed to inform policies to protect vulnerable populations. Objectives: To estimate heat and cold wave-related mortality risks in a cohort of veteran patients with chronic obstructive pulmonary disease (COPD) and explore disparities among strata of comorbidities, tobacco exposure, and urbanicity. Methods: We designed a time-stratified case-crossover study among deceased patients with COPD between 2016 and 2021 in the Veterans Health Administration system. Distributed lag models with conditional logistic regression estimated incidence rate ratios of heat and cold wave-associated mortality risk from lag days 0 to 3 for heatwaves and lag days 0 to 7 for cold waves. Attributable risks (ARs) per 100,000 patients were also calculated. Results: Of the 377,545 deceased patients with COPD, the largest heatwave-related mortality risk was in patients with COPD and asthma (AR, 14,016; 95% confidence interval [CI], -326, 30,706) across lag days 0 to 3. The largest cold wave-related mortality burden was in patients with COPD with no other reported comorbidities (AR, 1,704; 95% CI, 759, 2,686) across lag days 0 to 7. Patients residing in urban settings had the greatest heatwave-related (AR, 1,062; 95% CI, 576, 1,559) and cold wave-related (AR, 1,261; 95% CI, 440, 2,105) mortality risk (across lag days 0 to 1 and 0 to 7, respectively). There were no differences in mortality risk by tobacco exposure. Conclusions: Our findings show that individuals with COPD are susceptible to heat and cold waves. This information can inform clinical practice and public health policy about the mortality risk vulnerable populations experience with respect to extreme weather conditions. Furthermore, our results may be used in the development and refinement of future extreme weather warning systems designed for public health purposes.