OBJECTIVES: To characterize health-related quality of life (HRQoL) in patients with pulmonary arterial hypertension (PAH) in relation to persons of similar age and gender in the general United States (US) population. METHODS: Data were obtained from a large phase III clinical trial in which patients (n=274) were randomized to sildenafil or placebo for 12 weeks.  We characterized HRQoL using responses to the Short Form-36 General Health Survey (SF-36) obtained at baseline; the SF-36 addresses eight HRQoL domains: physical functioning (PF), role functioning–physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role functioning–emotional (RE), and mental health (MH).  Values for these eight domains were then standardized to US population norms for persons aged 45-54 years (mean age of patients in trial was 49 years). RESULTS: A total of 39% and 58% of patients were designated at baseline as Functional Class (FC) II and III, respectively (<1% and 3% were designated as FC I and IV), with 75% women.   Standardized mean scores were 30.4 for PF, 27.9 for RP, 47.8 for BP, 34.2 for GH, 41.2 for VT,  38.9 for SF, 34.9 for RE, and 43.7 for MH.  In comparison with the US population, whose mean score for each domain = 50, PF, RP, GH, SF, and RE were all substantially worse for PAH patients.  Additionally MH and VT were marginally worse among PAH patients, and BP was comparable to US norms. CONCLUSIONS: With the exception of bodily pain and mental health, PAH patients have substantially poorer SF-36 scores than their peers in the US general population, especially in terms of physical functioning, role functioning-physical, role functioning-emotional, and general health.