Background Photon-counting detector (PCD) CT provides comprehensive spectral data with every acquisition, but studies evaluating myocardial extracellular volume (ECV) quantification with use of PCD CT compared with an MRI reference remain lacking. Purpose To compare ECV quantification for myocardial tissue characterization between a first-generation PCD CT system and cardiac MRI. Materials and Methods In this single-center prospective study, adults without contraindication to iodine-based contrast media underwent same-day cardiac PCD CT and MRI with native and postcontrast T1 mapping and late gadolinium enhancement for various clinical indications for cardiac MRI (the reference standard) between July 2021 and January 2022. Global and midventricular ECV were assessed with use of three methods: single-energy PCD CT, dual-energy PCD CT, and MRI T1 mapping. Quantitative comparisons among all techniques were performed. Correlation and reliability between different methods of ECV quantification were assessed with use of the Pearson correlation coefficient (r) and the intraclass correlation coefficient. Results The final sample included 29 study participants (mean age ± SD, 54 years ± 17; 15 men). There was a strong correlation of ECV between dual- and single-energy PCD CT (r = 0.91, P < .001). Radiation dose was 40% lower with dual-energy versus single-energy PCD CT (volume CT dose index, 10.1 mGy vs 16.8 mGy, respectively; P < .001). In comparison with MRI, dual-energy PCD CT showed strong correlation (r = 0.82 and 0.91, both P < .001) and good to excellent reliability (intraclass correlation coefficients, 0.81 and 0.90) for midventricular and global ECV quantification, but it overestimated ECV by approximately 2%. Single-energy PCD CT showed similar relationship with MRI but underestimated ECV by 3%. Conclusion Myocardial tissue characterization with photon-counting detector CT-based quantitative extracellular volume analysis showed a strong correlation to MRI. © RSNA, 2023 Supplemental material is available for this article.