Background: Heroin smokers have high rates of COPD, respiratory morbidity, hospital admission, and mortality. We assessed the natural history of symptoms and lung function in this population over time. Methods: A cohort of heroin smokers with COPD was followed for 18 to 24 months. At baseline and follow-up, respiratory symptoms were measured by the Medical Research Council Dyspnea Scale (MRC) and the COPD Assessment Tool (CAT), and postbronchodilator spirometry was performed. Frequency of health-care-seeking episodes was extracted from routine health records. Parametric, nonparametric, and linear regression models were used to analyze the change in symptoms and lung function over time. Results: Of 372 participants originally recruited, 161 were assessed at follow-up (mean age, 51.0 ± 5.3 years; 74 women [46%]) and 106 participants completed postbronchodilator spirometry. All participants were current or previous heroin smokers, and 122 (75.8%) had smoked crack. Symptoms increased over time (MRC score increased by 0.48 points per year, P <.001; CAT score increased by 1.60 points per year, P <.001). FEV ₁ declined annually by 90 ± 190 mL (P <.001). This deterioration was not associated with change in tobacco or heroin smoking status or use of inhaled medications. Conclusions: Heroin smokers experience a high and increasing burden of chronic respiratory symptoms and a decline in FEV ₁ that exceeds the normal age-related decline observed among tobacco smokers with COPD and healthy nonsmokers. Targeted COPD diagnostic and treatment services hosted within opiate substitution services could benefit this vulnerable, relatively inaccessible, and underserved group of people.