The long-term oxygen therapy (LTOT) for patients with chronic obstructive pulmonary disease (COPD) has been shown to increase survival in patients with severe resting hypoxemia. The adherence to LTOT may also simultaneously affect the development of concomitant pulmonary hypertension (PH) due to COPD with hypoxemia. We retrospectively reviewed 276 cases of COPD with or without PH assessed by right heart catheterization (RHC) to investigate whether adherence to continuous LTOT had a prophylactic effect on the development of PH in a time interval of two years. In contrast to the patients in the non-compliance group (PH prevalence 64.2%), patients with excellent compliance of adhering to continuous LTOT > 15 h per day in the compliance group (PH prevalence 37.6%) are more liable to postpone the development of PH due to hypoxic COPD for at least two years. Adherence to LTOT ≥ 15 h/day is strongly recommended in order to lower the risk and delay the development of consequent PH in COPD with hypoxemia.