Abstract Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction and the mortality and morbidity of patients with HF with preserved ejection fraction (HFpEF) are high. However, there is no established therapy to improve survival in these patients. HFpEF patients are often elderly and their primary chronic symptom is severe exercise intolerance. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. A steep increase in left atrial pressure during exercise is an important cause of exertional dyspnea in HFpEF patients. The creation of a left-to-right interatrial shunt to decompress the left atrium may improve symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device (IASD) has been developed and evaluated in patients with HFpEF in several clinical trials. However, there is insufficient evidence regarding the benefit of transcatheter IASD in these patients. Methods: This meta-analysis will include randomized controlled trials and single-arm trials on the effects of transcatheter IASD on exercise capacity, HF symptoms, and health-related quality of life in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be exercise capacity (6-minute walking distance). The secondary outcomes will be HF symptoms, health-related quality of life, and mortality and hospitalization rates. Discussion: This meta-analysis will evaluate the effect of transcatheter IASD in HFpEF patients, providing evidence to the clinical use of transcatheter IASD in these patients. Systematic review registration: INPLASY202120025