There is no recommendation for treating pulmonary hypertension (PH) when associated with chronic obstructive pulmonary disease (COPD). To evaluate the effect of PH-specific therapy in patients with COPD. All successive patients with severe PH mean pulmonary arterial pressure (mPAP) ≥35 mm Hg and COPD, who received specific PH medication and who underwent right heart catheterization at baseline and after 3-12 months of treatment, were analyzed from a prospective database. Twenty-six patients were included with a median follow-up of 14 months. Mean forced expiratory volume in 1 s was 57 ± 20% of predicted, and mean forced expiratory volume in 1 s/forced vital capacity was 47 ± 12%. Dyspnea was New York Health Association classification stage (NYHA) II in 15%, NYHA III in 81% and NYHA IV in 4%. First-line treatments were endothelin receptor antagonists in 11 patients, phosphodiesterase-5 inhibitors in 11 patients, calcium blocker in 1 patient, combination therapy in 3 patients including 2 with a prostanoid. After 6 ± 3 months, pulmonary vascular resistance decreased from 8.5 ± 3 to 6.6 ± 2 Wood units (p < 0.001), with significant improvement of cardiac index from 2.44 ± 0.43 to 2.68 ± 0.63 liters × min × m-2 (p = 0.015) and mPAP from 48 ± 9 to 42 ± 10 mm Hg (p = 0.008). There was no significant difference in dyspnea, 6-min walking distance, echocardiographic parameters or N-terminal pro-brain natriuretic peptide levels. There was no significant difference in arterial oxygen saturation after 3-12 months of treatment. Specific PH medications may improve hemodynamic parameters in COPD patients with severe PH. Appropriate prospective randomized studies are needed to evaluate the potential long-term clinical benefit of treatment.