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Objectives High-resolution post-contrast T1-weighted imaging is a workhorse sequence in the evaluation of neurological disorders. The T1-MPRAGE sequence has been widely adopted for the visualization of enhancing pathology in the brain. However, this three-dimensional (3D) acquisition is lengthy and prone to motion artifact, which often compromises diagnostic quality. The goal of this study was to compare a highly accelerated wave-controlled aliasing in parallel imaging (CAIPI) post-contrast 3D T1-MPRAGE sequence (Wave-T1-MPRAGE) with the standard 3D T1-MPRAGE sequence for visualizing enhancing lesions in brain imaging at 3 T. Methods This study included 80 patients undergoing contrast-enhanced brain MRI. The participants were scanned with a standard post-contrast T1-MPRAGE sequence (acceleration factor [R] = 2 using GRAPPA parallel imaging technique, acquisition time [TA] = 5 min 18 s) and a prototype post-contrast Wave-T1-MPRAGE sequence (R = 4, TA = 2 min 32 s). Two neuroradiologists performed a head-to-head evaluation of both sequences and rated the visualization of enhancement, sharpness, noise, motion artifacts, and overall diagnostic quality. A 15% noninferiority margin was used to test whether post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE. Inter-rater and intra-rater agreement were calculated. Quantitative assessment of CNR/SNR was performed. Results Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE for delineating enhancing lesions with unanimous agreement in all cases between raters. Wave-T1-MPRAGE was noninferior in the perception of noise ( p < 0.001), motion artifact ( p < 0.001), and overall diagnostic quality ( p < 0.001). Conclusion High-accelerated post-contrast Wave-T1-MPRAGE enabled a two-fold reduction in acquisition time compared to the standard sequence with comparable performance for visualization of enhancing pathology and equivalent perception of noise, motion artifacts and overall diagnostic quality without loss of clinically important information. Key Points • Post-contrast wave-controlled aliasing in parallel imaging (CAIPI) T1-MPRAGE accelerated the acquisition of three-dimensional (3D) high-resolution post-contrast images by more than two-fold. • Post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE with unanimous agreement between reviewers (100% in 80 cases) for the visualization of intracranial enhancing lesions. • Wave-T1-MPRAGE was equivalent to the standard sequence in the perception of noise in 94% (75 of 80) of cases and was preferred in 16% (13 of 80) of cases for decreased motion artifact.