OBJECTIVES Pulmonary arterial hypertension (PAH) is defined as a chronic elevation of mean pulmonary arterial pressure above 25mm HGg and pulmonary resistance that can lead to right ventricular failure. Current PAH treatments reduce pulmonary vascular resistance. Tadalafil causes vaso-dilatation and long term remodeling of the pulmonary arteries by inhibiting phosphodiesterase type 5 (PDE5). The effects of Tadalafil on quality of life were assessed in patients with PAH. METHODS A double-blind clinical trial randomized 405 patients with PAH treated with placebo or oral Tadalafil at doses of 2.5, 10, 20, or 40 mg/d, most patients had idiopathic PAH, with symptoms in WHO functional class III. . At baseline and 16 weeks, quality of life was assessed using the Short Form 36 (SF-36) and EuroQol 5D (EQ-5D). Change from baseline to week 16 in the SF-36 domains and EQ-5D measures index scores and visual analog scale (VAS)] were tested using ANCOVA controlling for baseline randomization factors of each dose compare to Placebo separately. RESULTS All Tadalafil groups had significant improvement at 16 weeks in the Physical Functioning, Vitality, and Social Function domains of the SF-36. The Tadalafil 40 mg/d group also had significant improvement in the Role-Physical, Bodily Pain, and General Health domains compared with placebo (all P<0.01). For the EQ-5D, all Tadalafil groups had significantly greater utility index scores at 16 weeks, with the greatest improvement in the Tadalafil 40 mg/d group (P<0.0001 from placebo). Only the Tadalafil 40 mg/d group had an increase in VAS from baseline to 16 weeks compared with placebo (P<0.05). CONCLUSIONS Patients with PAH treated for 16 weeks with Tadalafil 40 mg/d had significant improvements in their quality of life, as measured by the SF-36 and EQ-5D, compared with placebo.