Traditional histological sectioning has been widely used to examine congenital heart defects (CHDs) in mouse models, providing detailed insights into tissue and cellular architecture. However, this approach is time-consuming, labor-intensive, and can miss subtle defects due to the critical need for precise serial sections. In contrast, three-dimensional imaging of cleared embryonic hearts using light sheet fluorescence microscopy offers a more efficient and comprehensive solution. This technique enables the rapid acquisition of z-stacks, including thousands of sections, without manual sectioning, which can be reconstructed into high-resolution 3D models. As a result, it significantly improves the detection and visualization of CHDs in mouse fetuses.