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The purpose of our study was to prospectively compare a recently developed method of isotropic 3D fast spin-echo (FSE) with extended echo-train acquisition (XETA) with 2D FSE and 2D fast recovery FSE (FRFSE) for MRI of the knee.Institutional review board approval, Health Insurance Portability and Accounting Act (HIPAA) compliance, and informed consent were obtained. We studied 10 healthy volunteers and one volunteer with knee pain using 3D FSE XETA, 2D FSE, and 2D FRFSE. Images were obtained both with and without fat suppression. Cartilage and muscle signal-to-noise ratio (SNR) and cartilage-fluid contrast-to-noise ratio (CNR) were compared using a Student's t test. We also compared reformations of 3D FSE XETA with 2D FSE images directly acquired in the axial plane.Cartilage SNR was higher with 3D FSE XETA (56.8 +/- 9 [SD]) compared with the 2D FSE (45.8 +/- 8, p0.01) and 2D FRFSE (32.5 +/- 5.3, p0.01). Muscle SNR was significantly higher with 3D FSE XETA (52.1 +/- 4.3) than 2D FSE (45.2 +/- 9, p0.01) and 2D FRFSE (23.6 +/- 6.2, p0.01). Fluid SNR was significantly higher for 2D FSE (144.9 +/- 33) than 3D FSE XETA (104.7 +/- 18, p0.01). Compared with 2D FSE and 2D FRFSE, 3D FSE XETA had lower cartilage-fluid CNR due to higher cartilage SNR (p0.01). Three-dimensional FSE XETA acquired volumetric data sets with isotropic resolution. Reformatted images in the axial plane were similar to axial 2D FSE acquisitions but with thinner slices.Three-dimensional FSE XETA acquires high-resolution (approximately 0.7 mm) isotropic data with intermediate and T2-weighting that may be reformatted in arbitrary planes. Three-dimensional FSE XETA is a promising technique for MRI of the knee.