Background— Fluoroscopy and transesophageal echocardiography (TEE) are used to guide transcatheter left atrial appendage (LAA) closure in patients with atrial fibrillation to prevent thromboembolic events. This study examines whether real-time three-dimensional volume ICE guidance (4D volume ICE) can be used as an alternative to TEE during LAA closure (LAAC). Methods and Results— Fifteen patients with atrial fibrillation (AF), who had high risk for stroke and contraindication for long-term warfarin therapy, were enrolled in the study. The WATCHMANTM device was used for transcatheter LAAC under fluoroscopy. LAA and device sizing was performed using TEE and right atrial ICE. Intraprocedural ICE measurements were consistent with TEE; LAA maximal width and depth, and maximal diameter of the implanted device were moderately correlated (Pearson’s coefficient: 0.63, 0.65, and 0.71 respectively; p<0.05) with good agreement (bias: -0.03 cm, -0.07 cm, and 0.003 cm respectively). The average imaging success rate, defined by the number of patients with all the required intraprocedural measurements, was 67% for right atrial ICE and 100% for TEE. The WATCHMAN device was successfully implanted in all patients with a device to patient ratio of 1.33. Conclusions— Right atrial 4D volume ICE imaging can be used as an intraprocedural sizing and guidance tool for transcatheter LAAC with measurements comparable to TEE. Challenging patient characteristics significantly degrade the image quality when imaging from the right atrium. Standardized workflow with proper patient selection and optimal preprocedural planning may improve the diagnostic quality of right atrial volume ICE guidance for transcatheter LAAC procedure.