Background and objective Interstitial lung diseases (ILD) are often associated with pulmonary hypertension (PH). This study aimed to evaluate the therapeutic benefit of phosphodiesterase-5 (PDE-5) inhibitors in pulmonary hypertension secondary to ILD. Methods Patients with ILD and PH were treated with sildenafil or tadalafil. Right heart catheterization was performed before and after a minimum of 3-month treatment. In addition, lung function, 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration were assessed. Results Ten ILD patients (three female, mean age 64.4 +/- 9.0 years, six with idiopathic pulmonary fibrosis (IPF), four with hypersensitivity pneumonitis, (HP)) with significant precapillary PH (mean pulmonary artery pressure (PAPm)25mmHg, pulmonary vascular resistance (PVR)>280 dyn*s*cm-5; pulmonary artery wedge pressure (PAWPm)15mmHg) were treated with either sildenafil (n=5) or tadalafil (n=5). Pulmonary haemodynamics were severely impaired at baseline (PAPm 42.9 +/- 5.4mmHg; cardiac index (CI) 2.7 +/- 0.6 L/min/m2; PVR 519 +/- 131 dynxsecxcm-5). After mean follow-up of 6.9 +/- 5.8 months an increase in CI (2.9 +/- 0.7 L/min/m2, P=0.04) and a decrease in PVR (403 +/- 190 dynxsecxcm-5, P=0.03) were observed. 6MWD and BNP did not change significantly. Conclusions Our data suggest that treatment with PDE-5 inhibitors improves pulmonary haemodynamic patients with PH secondary to ILD.