Background: Sotatercept, a first-in-class activin-signaling inhibitor, demonstrated efficacy in pulmonary arterial hypertension (PAH) in the pivotal PULSAR and STELLAR trials. However, whether these benefits and the drug’s distinct safety profile translate to routine clinical practice in the treatment of idiopathic PAH remains unclear. Methods: We conducted a retrospective study using the TriNetX global health research network. Adult patients with idiopathic PAH treated with standard-of-care (SoC) background therapies were identified. Those receiving add-on sotatercept were matched 1:1 with patients on background therapy alone using propensity score matching. Results: A total of 1378 matched patients (689 per arm) were included. The median follow-up was 13.8 months for the SoC group and 10.3 months for the sotatercept group; therefore, the analysis was limited to up to 12 months. Sotatercept was associated with a 49% reduction in the risk of all-cause mortality (HR = 0.51, p = 0.002). A significant reduction was observed in all-cause hospitalizations for the sotatercept arm (HR = 0.44; 12-month rate 6.3% vs. 11.5%, p = 0.010). Safety analysis revealed 2.5-fold increased odds of epistaxis (OR = 2.68, p < 0.001) and 4-fold increased odds of erythrocytosis (OR = 4.26, p < 0.001) with sotatercept, while thrombocytopenia rates were similar (OR = 0.98, p = 0.946). Sotatercept seems to be associated with a higher risk of hypertension compared to background therapy alone (OR = 1.85, p = 0.155). Conclusions: In this large real-world cohort, the addition of sotatercept to SoC background therapy significantly improved survival in idiopathic PAH. While bleeding events, erythrocytosis and elevated blood pressure seemed to be more frequent with sotatercept, the overall safety profile was acceptable, suggesting that the substantial survival and hospitalization benefits outweigh these risks in routine clinical practice.