BACKGROUND: Silicon photomultiplier-positron emission tomography (SiPM-PET) has better sensitivity, spatial resolution, and timing resolution than photomultiplier tube (PMT)-PET. The present study aimed to clarify the advantages of SiPM-PET in 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) brain imaging in a head-to-head comparison with PMT-PET in phantom and clinical studies. METHODS: Contrast was calculated from images acquired from a Hoffman 3D brain phantom, and image noise and uniformity were calculated from images acquired from a pool phantom using SiPM- and PMT-PET. Sequential PMT-PET and SiPM-PET [18F]FDG images were acquired over a period of 10 min from 22 controls and 10 patients. All images were separately normalized to a standard [18F]FDG PET template, then the mean standardized uptake values (SUVmean) and Z-score were calculated using MIMneuro and CortexID Suite, respectively. RESULTS: Image contrast, image noise, and uniformity in SiPM-PET changed 19.2, 3.5, and - 40.0% from PMT-PET, respectively. These physical indices of both PET scanners satisfied the criteria for acceptable image quality published by the Japanese Society of Nuclear Medicine of contrast > 55%, CV ≤ 15%, and SD ≤ 0.0249, respectively. Contrast was 70.0% for SiPM-PET without TOF and 59.5% for PMT-PET without TOF. The TOF improved contrast by 3.5% in SiPM-PET. The SUVmean using SiPM-PET was significantly higher than PMT-PET and did not correlate with a time delay. Z-scores were also significantly higher in images acquired from SiPM-PET (except for the bilateral posterior cingulate) than PMT-PET because the peak signal that was extracted by the calculation of Z-score in CortexID Suite was increased. The hypometabolic area in statistical maps was reduced and localized using SiPM-PET. The trend was independent of whether the images were derived from controls or patients. CONCLUSIONS: The improved spatial resolution and sensitivity of SiPM-PET contributed to better image contrast and uniformity in brain [18F]FDG images. The SiPM-PET offers better quality and more accurate quantitation of brain PET images. The SUVmean and Z-scores were higher in SiPM-PET than PMT-PET due to improved PVE. [18F]FDG images acquired using SiPM-PET will help to improve diagnostic outcomes based on statistical image analysis because SiPM-PET would localize the distribution of glucose metabolism on Z-score maps.