Chronic obstructive pulmonary disease is a chronic, often progressive disease, which in most patients is caused by tobacco smoking. Our study focuses on differences in COPD-related outcomes between never smokers, former smokers, and current smokers. A nationwide, population-based cohort study utilizing Danish health registries. Clinical and socioeconomic variables including smoking status, comorbidities, and dyspnea were obtained. Poisson and Cox Regression were used to calculate the impact of these clinical parameters on the risk of moderate and severe exacerbations and mortality during 12 months of follow-up. A total of 49,826 patients ≥40 years of age, with a hospital diagnosis of COPD in 2008-2017, were identified (mean age 69.2 years, 52% females). A total of 2127 (4%) were never smokers, 29,854 (60%) were former smokers and 17,845 (36%) current smokers. Compared to former and current smokers, never smokers reported a lower modified Medical Research Council score and had a milder COPD stage according to the Global Initiative for Chronic Obstructive Lung Disease classification. During follow-up, never smokers had a significantly lower risk of severe exacerbations (hazard ratio 0.87, 95% confidence interval [CI] 0.78-0.97) and a lower rate of death (mortality ratio 0.75, 95% CI 0.70-0.81) compared to patients with a smoking history. Our nationwide study showed that COPD in never smokers is characterized by a lower level of dyspnea, milder lung function impairment, and a lower risk of exacerbations and death. At the same time, we found active smokers to have the highest risk. These findings highlight the need for campaigns to prevent smoking and may help general practitioners as well as other health care professionals to motivate patients with COPD to stop smoking.