Mineralocorticoid receptor (MR) antagonists are well established in the treatment of chronic left heart disease, however, there is an ever growing body of evidence suggesting potential benefits in other cardiovascular disease. Here, we evaluated the effects of MR antagonists on hypoxia-induced pulmonary hypertension, a progressive disease that is associated with poor outcomes. We could show that MR antagonists or MR deletion from endothelial cells likewise improved pulmonary vascular remodeling and subsequent right heart failure. In contrast, MR deletion from smooth muscle cells, fibroblasts, or macrophages had no significant effect.