Objectives QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. Methods Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. Results The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. Conclusions QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. Key Points • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.