This study aims to evaluate the safety and feasibility of obtaining wedged pulmonary artery (PA) samples and investigate the differential vascular beds' distribution of select inflammatory and cellular adhesion molecules that are implicated in pulmonary arterial hypertension (PAH) pathogenesis. This is a cross-sectional study of adult patients. Serum samples were simultaneously drawn from three different vascular sites during right heart catheterization as part of PAH evaluation: The superior vena cava, distal pulmonary artery prior to wedging, and distal pulmonary artery after (and distal to) wedging. The study group was comprised of patients with either PAH or chronic thromboembolic pulmonary hypertension (i.e., WHO/Dana Point Group 1 or 4). The internal control group included patients whose hemodynamics were not consistent with pulmonary hypertension. The external control group consisted of healthy volunteers who had a peripheral venous sample drawn. The mean age of the 25 study patients was 55 ± 14 years and mean BMI was 31 ± 10, and those of the 25 internal control patients were 49 ± 14 years and 26 ± 5, respectively. There were no complications resulting from obtaining wedged PA samples. Obtaining adequate wedged samples was successful in 80% of patients. More severe pulmonary hypertension was associated with lower success rates. There were no significant differences in the concentrations of the different biomarkers studied amongst the different vascular sites (n = 25 study patients). There was a nonsignificant trend of decreasing biomarkers concentrations from peripheral to wedged to un-wedged PA samples. Compared to the healthy external controls, sVCAM-1 levels were higher in the study group. Obtaining wedged PA blood samples is safe and feasible in adult patients with pulmonary hypertension. There were no differences in the distribution of markers between the vascular beds within patients.