OBJECTIVES: This study presents a single-site experience of 5 patients with severe tricuspid regurgitation (TR) who underwent implantation of a novel transcatheter tricuspid valve replacement device. BACKGROUND: Functional TR is the most common etiology of severe TR in the developed world and is associated with unfavorable clinical outcomes. Although numerous transcatheter repair devices are currently in early clinical trials, most result in incomplete degrees of TR reduction and functional improvement. METHODS: Transcatheter tricuspid valve replacement was performed in 5 patients with compassionate use of the novel GATE System. All patients had symptomatic, massive and/or torrential TR at baseline. All patients had computed tomography, transthoracic and transesophageal echocardiographic assessment of the tricuspid valve and right heart anatomy. All patients had a surgical transatrial approach performed with valve implantation guided by fluoroscopy and intraprocedural transesophageal echocardiography. RESULTS: Baseline characteristics of the patients showed a substantial burden of comorbidities. All patients had successful implantation of the transcatheter valve, with significant reduction of TR to ≤2+. Baseline poor right ventricular (RV) function measured by global longitudinal strain and RV change in pressure divided by change in time were associated with post-implantation RV failure and poor clinical outcomes in this small group. Four of the 5 patients were followed for 3 to 6 months following the initial implantation and showed evidence of RV remodeling, increased cardiac output, and reduction in New York Heart Association functional class. CONCLUSIONS: Implantation of a first-generation TTVR device was technically feasible in patients with more than severe TR. Transcatheter tricuspid valve replacement was associated with RV remodeling, increased cardiac output, and improvement in New York Heart Association functional class in most patients. Further studies are needed to refine patient population selection for this device and to determine long-term outcomes.