Left atrial decompression (LAD) using transseptal puncture followed by balloon atrial septostomy recently has been described as a palliative minimally invasive procedure in dogs with advanced degenerative mitral valve disease (DMVD). We report herein the first use of intracardiac echocardiography (ICE) guidance combined with 3-dimensional transesophageal echocardiography (3D-TEE) to ensure the safety of the LAD procedure from a caudal approach, as performed in humans, in 2 American College of Veterinary Internal Medicine (ACVIM) stage C and D DMVD dogs (Jack Russell Terrier and Cavalier King Charles Spaniel) with recurrent episodes of acute pulmonary edema. Both LAD procedures were successful, as confirmed by markedly decreased systolic left atrial pressures (17 and 25 mmHg vs. 42 and 80 mmHg before LAD, respectively). Both dogs remained free of left-sided congestive heart failure signs for 8 and 10 months, respectively. The addition of ICE guidance to 3D-TEE is feasible and valuable in medium-sized dogs for safe LAD procedures.