OBJECTIVES: Lengthened survival in pulmonary arterial hypertension (PAH) has shifted attention towards disease burden that PAH imposes on patients and healthcare systems. Currently, most available studies emphasize epidemiology, clinical characteristics and medications of PAH; while large observational studies reporting real-world health-related quality-of-life (HRQOL) of patients with PAH are lacking. Thus this study aims to study real-world HRQOL of patients with PAH, and summarise factors influencing it. METHODS: Systematic literature searches were conducted in English-language databases (PubMed, Web of Knowledge, ScienceDirect and OVID) and Chinese-language databases (China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP and SinoMed) to identify observational studies (2000-2015) assessing HRQOL of patients with PAH. Search results were independently reviewed and extracted by two reviewers who then evaluated the study quality. RESULTS: Of 3392 records identified in initial search, 20 eligible papers (19 English, 1 Chinese) were finally included. Studies used a range of instruments; the generic 36-item Short Form Survey (SF-36) was the most widely-used, followed by disease-specific Cambridge Pulmonary Hypertension Outcome Survey (CAMPHOR). Mean HRQOL scores assessed by SF-36 (physical component summary: 25.4-80.1; mental component summary: 33.2-76.0) and CAMPHOR (symptom scores: 3.1-17; total HRQOL: 2.8-12.6; activity scores: 3.8-18.1) varied across studies, reporting decreased physical, emotional and overall HRQOL in patients. Patients experienced a constellation of profound symptoms even with optimal PAH therapy, including dyspnea with activity, fatigue and sleep difficulty. Mental health (depression, anxiety, stress), physical health (exercise capacity, symptoms) and medical therapies were reported to affect HRQOL. CONCLUSIONS: The disease burden of PAH is substantial regarding decreased HRQOL of patients. Opportunities for improvement exist with advanced new treatments and improved disease management. The paucity of large observational evidence in this area requires researchers' attention, especially in China.