The purpose of this study was to compare contrast-enhanced MRI with dual-radionuclide SPECT for the detection of myocardial damage associated with hypertrophic cardiomyopathy. Twenty-three patients with hypertrophic cardiomyopathy were examined. Delayed hyperenhancement of the damaged myocardium was observed using contrast-enhanced MRI, and regional wall thickness and left ventricular ejection fraction were measured using cine balanced steady-state free precession MRI. Dual-radionuclide SPECT using technetium-99m sestamibi and iodine-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was performed at rest. In the abnormal myocardial segments, agreement between the contrast-enhanced MRI and 123I BMIPP SPECT was assessed. The relationships between the regional and global cardiac abnormalities and the delayed hyperenhancement on MRI and decreased uptake of 123I BMIPP were also evaluated. In 368 left ventricular segments, 57 segments showed delayed hyperenhancement on MRI, 43 segments showed decreased uptake of 123I BMIPP, and seven showed decreased uptake of (99m)Tc sestamibi. The delayed hyperenhancement and decreased uptake of 123I BMIPP were frequently observed in the interventricular septal wall (p < 0.0001); however, the agreement between the methods in detecting myocardial abnormalities was fair (kappa = 0.38). The abnormal septal walls were significantly thicker than those without apparent abnormalities (p = 0.031). There was an inverse correlation between the number of enhancing segments and the ejection fraction (r = -0.53). In hypertrophic cardiomyopathy, contrast-enhanced MRI was valuable for the detection of extensive myocardial damage.