Recent technical developments have significantly increased the signal-to-noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole-brain high-resolution perfusion imaging, combining pseudo-continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in-plane k-space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in-plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack-Of-Spirals). High-resolution perfusion images (2 × 2 × 4 mm(3) ) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray-to-white matter contrast. Point-spread-function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in-plane segmented 3D readouts and BS provided high-SNR high-resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack-Of-Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through-plane blurring due to its inherent oversampling of the central k-space region, its reduced effective TE and shorter total readout time, at the expense of a slight increase in the effective in-plane voxel size.