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Purpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH., Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility., Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications., Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients., Competing Interests: Dr Charles Burger reports personal fees from Janssen, personal fees from INSMED, personal fees from Merck, and non-financial support from United Therapeutics, during the conduct of the study. Yuen Tsang is a former employee and owns stock in Johnson & Johnson. Dr Marie Chivers, Nikki Atkins and Ms Riya Vekaria report employment with Avalere Health which was in receipt of payment from Janssen for this element of the study. Dr Gurinderpal Doad and Dr Sumeet Panjabi are employees and stockholders of Johnson & Johnson, the company that markets oral selexipag. The authors report no other conflicts of interest in this work., (© 2024 Burger et al.)