A method and system for left ventricle (LV) endocardium surface segmentation using constrained optimal mesh smoothing is disclosed. The LV endocardium surface in the 3D cardiac volume is initially segmented in a 3D cardiac volume, such as a CT volume, resulting in an LV endocardium surface mesh. A smoothed LV endocardium surface mesh is generated by smoothing the LV endocardium surface mesh using constrained optimal mesh smoothing. The constrained optimal mesh smoothing determines an optimal adjustment for each point on the LV endocardium surface mesh by minimizing an objective function based at least on a smoothness measure, subject to a constraint bounding the adjustment for each point. The adjustment for each point can be constrained to prevent adjustments inward toward the blood pool in order to ensure that the smoothed LV endocardium surface mesh encloses the entire blood pool.