AbstractPatients treated for drug addiction have high asthma and COPD prevalence rates. The relative contributions of cigarette smoking, smoking intensity and possible smoking of other substances has not been described. We aimed to describe the prevalence and determinants of asthma and COPD in patients prescribed methadone as opioid substitution therapy (OST). In a cross-sectional study of an anonymised patient-level primary care dataset of UK inner-city general practices (n = 46), 321,395 patients aged ≥18 years were identified. A total of 676 (0.21%) had a record of a methadone ever issued in primary care. The association between respiratory disease and methadone prescribing was examined using logistic regression. Models were adjusted for potential effects of clustering by practice. A total of 97.3% of patients prescribed methadone were cigarette smokers, either current (81.2%) or ex-smokers (16.1%). The prevalences of asthma and COPD were higher in methadone patients (14.2% and 12.4%, respectively) compared to non-methadone patients (4.4% and 1.1%, respectively). Methadone was an independent determinant of asthma, adjusting for smoking status (OR 3.21; 95% CI: 2.52, 4.10) or for smoking intensity (3.08; 2.27, 4.19), and of COPD, adjusting for smoking status (6.00; 4.61, 7.80) or for smoking intensity (5.80; 4.12, 8.17). COPD and asthma prevalence were substantially higher in those prescribed methadone compared to those never prescribed methadone. Prescription of methadone was an independent predictor for both COPD and asthma, even after adjustment for smoking status and smoking intensity. Possible explanations include confounding by association with smoking of heroin or crack cocaine, both of which may have a causal association with COPD and asthma.