The purpose of this work is to devise and demonstrate an encoding strategy for 3D MRI that reconciles high speed with flexible segmentation, uniform k-space density, and benign T * 2 effects. Methods: Fast sampling of a 3D k-space is typically accomplished by 2D readouts per shot using EPI trains or spiral readouts. Tilted hexagonal (T-Hex) sampling is a way of acquiring more k-space volume per excitation while maintaining uniform sampling density and a smooth T * 2 filter. The k-space volume covered per shot is controlled by the tilting angle. Image reconstruction is performed with a 3D extension of the iterative SENSE approach, incorporating actual field dynamics and static off-resonance. T-Hex imaging is compared with established 3D schemes in terms of speed and noise performance. Results: Tilted hexagonal acquisition is found to achieve greater imaging speed than known alternatives, particularly in combination with spiral trajectories. The interplay of the proposed 3D trajectories, array detection, and off-resonance is successfully addressed by iterative inversion of the full signal model. Enhanced coverage per shot is of greatest utility for high speed in an intermediate resolution regime of 1 to 4 mm. T-Hex EPI combines the benefits of extended coverage per shot with increased robustness against off-resonance effects. Conclusion: Sampling of tilted hexagonal grids is a feasible means of gaining 3D imaging speed with near-optimal SNR efficiency and benign depiction properties. It is a particularly promising technique for time-resolved applications such as fMRI. K E Y W O R D S 3D encoding, algebraic image reconstruction, magnetic field monitoring, spiral imaging F I G U R E 1 Examples of 3D readout strategies: Concentric shells, yarnball, and interleaved multiplanar spirals. Black dots indicate that interleaves were omitted for better visibility | 2509 ENGEL Et aL.