Pulmonary arterial hypertension (PAH) patients with cardiopulmonary comorbidities have been prevalent nowadays. However, there was limited data on clinical characteristics and therapeutic responses in these populations.Patients diagnosed with right heart catheterization (RHC)-confirmed PAH between October 2021 to March 2023 were included in our study. According to whether they had cardiopulmonary diseases or not, they were classified into two groups: comorbidities group and non-comorbidities group. We aimed to compare the clinical data, PAH-targeted strategies, and therapeutic responses between these two PAH groups. We further analyzed the impact of the numbers and categories of comorbidities on therapeutic responses.Almost half of the patients co-existed with cardiopulmonary diseases. Compared with non-comorbidities group (n = 40), comorbidities group (n = 36) were senior (p = 0.000) and male predominantly (p = 0.005). Comorbidities group also associated inconsistencies between hemodynamics and 6-min walking distance (6MWD), with a shorter 6MWD (p = 0.000), but a lower mean pulmonary artery pressure (mPAP) (p = 0.008). Non-comorbidities group showed an upturn in the WHO-FC (p = 0.010) and risk assessment (p = 0.033), while the improvement of hemodynamics [decreased mPAP (p = 0.009) and pulmonary vascular resistance (PVR) (p = 0.001), increased cardiac index (p = 0.001)] in comorbidities group did not match the change in clinical severity (no significant improvements in WHO-FC, risk stratification and 6MWD). When categorized by the comorbidities counts, it demonstrated that the more comorbidities, the more severe the clinical conditions, and the worse the therapeutic responses.PAH patients with cardiopulmonary comorbidities represent a unique phenotype, with different clinical manifestation and treatment responses from typical PAH and inconsistencies between hemodynamics and functional status from baseline to follow-up.© 2025. The Author(s).