Patients with chronic obstructive pulmonary disease (COPD) who develop pulmonary hypertension (PH) have worse mortality than those with COPD alone. Predictors of poor outcomes in COPD-PH are not well described. Diffusing capacity of the lung (DLCO) assesses the integrity of the alveolar-capillary interface and thus may be a useful prognostic tool among those with COPD-PH.Using a single center registry, we sought to evaluate DLCO as a predictor of mortality in a cohort of COPD-PH patients.This retrospective cohort study analyzed 71 COPD-PH patients from the Johns Hopkins Pulmonary Hypertension Registry with right heart catheterization (RHC)-proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. Transplant-free survival was calculated from index RHC. Adjusted transplant-free survival was modelled using Cox proportional hazard methods, with age, pulmonary vascular resistance (PVR), FEV1, oxygen use, and N-terminal pro-brain natriuretic peptide (NT-proBNP) included as covariates.Overall unadjusted transplant-free 1-, 3-, and 5-year survival was 87%, 60%, and 51% respectively. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and PVR. Severe DLCO impairment was associated with poorer survival (log-rank ꭕ2 13.07, p<0.001), and adjusting for covariates, for every percent predicted decrease in DLCO, mortality increased by 4% (HR 1.04; 95% CI:1.01-1.07).Among patients with COPD-PH, severe gas transfer impairment is associated with higher mortality, even when adjusting for airflow obstruction and hemodynamics, suggesting that DLCO may be a useful prognostic marker in this population. Future studies are needed to further investigate the association between DLCO and morbidity, and to determine the utility of DLCO as a biomarker for disease risk and severity in COPD-PH.