Background: Determination of inter-method differences between clinically available volumetry methods are essential for the clinical application of brain volumetry in a wider context. Purpose: The purpose of this study was to examine the inter-method reliability and differences between the Siemens morphometry (SM) software and the NeuroQuant (NQ) software. Materials and Methods: MR images of 86 subjects with subjective or objective cognitive impairment were included in this retrospective study. For this study, 3D T1 volume images were obtained in all subjects using a 3T MR scanner (Skyra 3T, Siemens). Volumetric analysis of the 3D T1 volume images was performed using SM and NQ. To analyze the inter-method difference, correlation, and reliability, we used the paired t-test, Bland-Altman plot, Pearson's correlation coefficient, intraclass correlation coefficient (ICC), and effect size (ES) using the MedCalc and SPSS software. Results: SM and NQ showed excellent reliability for cortical gray matter, cerebral white matter, and cerebrospinal fluid; and good reliability for intracranial volume, whole brain volume, both thalami, and both hippocampi. In contrast, poor reliability was observed for both basal ganglia including the caudate nucleus, putamen, and pallidum. Paired comparison revealed that while the mean volume of the right hippocampus was not different between the two software, the mean difference in the left hippocampus volume between the two methods was 0.17 ml (P < 0.001). The other brain regions showed significant differences in terms of measured volumes between the two software. Conclusion: SM and NQ provided good-to-excellent reliability in evaluating most brain structures, except for the basal ganglia in patients with cognitive impairment. Researchers and clinicians should be aware of the potential differences in the measured volumes when using these two different software interchangeably.