The purpose of this study was to develop criteria for predicting survival and clinical improvement with long-term domiciliary home oxygen therapy (LTDO2) in patients with both chronic obstructive pulmonary disease (COPD) and cor pulmonale (CP). Twenty-eight such patients were divided into 2 groups, responders (R) and nonresponders (NR), on the basis of the fall in their mean pulmonary artery pressure (delta PAP) while breathing 28% O2 for 24 h. The R(n = 17) and NR (n = 11) had delta PAP greater than and lesser than 5 mmHg, respectively. Eighty-eight percent of the R, but only 22% of the NR, were alive at the end of 2 yr of LTDO2. Eighty-five percent of R, but only 11% of NR, achieved an end-exercise maximal oxygen consumption (max VO2) greater than 6.5 ml min-1 kg-1. Left ventricular ejection fraction improved while breathing O2 for 48 h in the R only. The NR and R were similar in all other respects. We conclude that delta PAP greater than 5 mmHg and/or max VO2 6.5 ml min-1 kg-1 or greater predict 2-yr survival with LTDO2 in patients with COPD and CP, and it can be useful in planning their management.