Background: Pulmonary arterial hypertension (PAH) may complicate both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). These two conditions, however, frequently coexist in the same patient (HIV/Po-PAH). We evaluated clinical, functional, hemodynamic characteristics and prognostic parameters of these three groups of patients. Methods: We included patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to a single center. We compared clinical, functional and hemodynamic parameters, severity of liver disease [Child–Turcotte–Pugh (CTP) and Model for End-stage Liver Disease-Na (MELD-Na) scores], CD4 count and highly active antiretroviral therapy (HAART) administration. Prognostic variables were identified through Cox-regression analysis. Results: Patients with Po-PAH (n= 128) were the oldest, patients with HIV-PAH (n= 41) had the worst hemodynamic profile and patients with HIV/Po-PAH (n= 35) had the best exercise capacity. Independent predictors of mortality were age and CTP score for Po-PAH, HAART administration for HIV-PAH, MELD-Na score and hepatic venous-portal gradient for HIV/Po-PAH. Conclusions: Patients with HIV/Po-PAH are younger and have a better exercise capacity than patients with Po-PAH, have a better exercise capacity and hemodynamic profile compared to patients with HIV-PAH, and their prognosis seems to be related to the hepatic disease rather than to HIV infection. The prognosis of patients with Po-PAH and HIV-PAH seems to be related to the underlying disease.