Abstract Objective The aim of this study was to compare brain perfusion SPECT obtained from a 360° CZT and a conventional Anger camera. Methods The 360° CZT camera utilizing a brain configuration, with 12 detectors surrounding the head, was compared to a 2-head Anger camera for count sensitivity and image quality on 30-min SPECT recordings from a brain phantom and from 99m Tc-HMPAO brain perfusion in 2 groups of 21 patients investigated with the CZT and Anger cameras, respectively. Image reconstruction was adjusted according to image contrast for each camera. Results The CZT camera provided more than 2-fold increase in count sensitivity, as compared with the Anger camera, as well as (1) lower sharpness indexes, giving evidence of higher spatial resolution, for both peripheral/central brain structures, with respective median values of 5.2%/3.7% versus 2.4%/1.9% for CZT and Anger camera respectively in patients ( p < 0.01), and 8.0%/6.9% versus 6.2%/3.7% on phantom; and (2) higher gray/white matter contrast on peripheral/central structures, with respective ratio median values of 1.56/1.35 versus 1.11/1.20 for CZT and Anger camera respectively in patients ( p < 0.05), and 2.57/2.17 versus 1.40/1.12 on phantom; and (3) no change in noise level. Image quality, scored visually by experienced physicians, was also significantly higher on CZT than on the Anger camera (+ 80%, p < 0.01), and all these results were unchanged on the CZT images obtained with only a 15 min recording time. Conclusion The 360° CZT camera provides brain perfusion images of much higher quality than a conventional Anger camera, even with high-speed recordings, thus demonstrating the potential for repositioning brain perfusion SPECT to the forefront of brain imaging.