Abstract Echocardiography is an excellent tool for visualizing heart anatomy and function, however inadequate and suboptimal visualization of the heart is becoming problematic as the overweight and obese population in the United States has increased dramatically over the last two decades. Inadequate or suboptimal visualization of the heart leads to increased exam time, decreased patient throughput, diminished quality or indeterminate diagnosis, and possible referral of the patient to other imaging procedures. These additional and alternative imaging methods can increase the costs associated with care and can potentially require the patient to have invasive or hazardous imaging procedures. We have previously developed a new ultrasonic imaging method, called Harmonic Spatial Coherence (HSC) imaging, that greatly enhances image quality by suppressing noise in the ultrasound image that is typically encountered in difficult-to-image patients. This is particularly important to echocardiography, in which diagnoses of cardiac anatomy and function are unobtainable in 12–64% of conventional echocardiograms. We have previously developed a prototype ultrasound imaging system that can display HSC images in real-time and have used this system to show that HSC imaging is vastly superior to conventional tissue harmonic imaging (THI) in visualizing the interior borders of the heart (i.e. the endocardium). In this project, we propose to translate our HSC imaging technique to clinical use in echocardiography by developing techniques to enable HSC imaging on a modern clinical ultrasound system. We propose to utilize this system in a large clinical study over two institutions to demonstrate its utility in clinically meaningful tasks and measurements. In addition, we propose development of several strategies that will enable easier implementation of this technique on modern ultrasound scanners. These strategies will reduce its computational burden and enable it to be applied to a wide array of modern scanners. In addition, these strategies should allow HSC to be applied to 3D echocardiography, an increasingly utilized modality due to the availability of high-quality matrix transducers. The outcome of this work will yield an imaging solution for the difficult-to-image patient that can be rapidly deployed across modern ultrasound imaging systems and echocardiography clinics.