Diagnostic yield of endomyocardial biopsy is low, particularly in disease that affects the myocardium in a nonuniform distribution. The authors hypothesized that real-time MRI guidance could improve the yield through targeted biopsy of focal myocardial pathology. They tested this hypothesis in an animal model of focal myocardial pathology using intracoronary ethanol and microspheres. The authors compared real-time MRI-guided endomyocardial biopsy in swine using a custom actively visualized MRI bioptome against x-ray–guided biopsy using a commercial bioptome by skilled operators. Real-time MRI guidance significantly increased the diagnostic yield of endomyocardial biopsy.