Mitral regurgitation (MR) is among the most common valvular heart diseases in clinics. MR induces volume overload of the heart and leads to heart failure (HF). Because physiological and molecular mechanisms in nonischemic HF are distinct from that of ischemic HF, a clinically relevant animal model of nonischemic HF is important for understanding the pathophysiology and developing new therapeutics targeting this HF phenotype. Additionally, the large animal model of MR provides opportunities to test new surgical and percutaneous approaches for correcting mitral valve insufficiency. In this chapter, we describe protocols for inducing MR in pigs using percutaneous approaches. Specifically, mitral valve chords are cut by a cardiac biopsy catheter inserted either antegrade (transseptal through venous access) or retrograde (arterial access) into the left ventricle. Both acute and chronic HF can be induced using this technique, and left atrial enlargement can be found at the chronic stage.