Objectives: To test the hypothesis that MRI of the ankle with a 10-min 3D CAIPIRINHA SPACE TSE protocol is at least equivalent for the detection of painful conditions when compared to a 20-min 2D TSE standard of reference protocol. Methods: Following institutional review board approval and informed consent, 70 symptomatic subjects underwent 3T MRI of the ankle. Six axial, sagittal and coronal intermediate-weighted (IW) and fat-saturated T2-weighted (T2FS) 2D TSE (total acquisition time, 20 min), and two sagittal isotropic IW and T2FS 3D CAIPIRINHA TSE (10 min) pulse sequence prototypes were obtained. Following randomization and anonymization, two musculoskeletal radiologists evaluated the 2D and 3D datasets independently. Descriptive statistics, inter-reader reliability, inter-method concordance, diagnostic definitiveness tests were applied. P-values < 0.05 were considered significant. Results: Raters diagnosed 116 cartilage defects with 2D and 109 with 3D MRI, 35 ligament tears with 2D and 65 with 3D MRI, 18 tendon tears with 2D and 20 with 3D MRI, and 137 osseous abnormalities with 2D and 149 with 3D MRI. The inter-reader agreement was high for 2D (Kendall W, 0.925) and 3D MRI (W, 0.936) (p < 0.05), as was the inter-method concordance (W, 0.919). The diagnostic definitiveness of readers was higher for 3D MRI than 2D MRI in 10-27% of the time, while the reverse was true in 7-11% of the time (p < 0.01). Conclusions: The performance of 10-min 3D CAIPIRINHA SPACE MRI for the detection of painful ankle conditions is similar to that of a 20-min 2D TSE MRI reference standard. Key Points: • CAIPIRINHA Acceleration facilitates isotropic 3D MRI of the Ankle in 10 min. • 10-min 3D CAIPIRINHA MRI and 20-min 2D TSE MRI have similar performance. • 3D CAIPIRINHA SPACE MRI afforded higher diagnostic definitiveness of readers.