AbstractFundamental and clinical neuroscience has benefited tremendously from the development of automated computational analyses. In excess of 600 human neuroimaging papers using Voxel-based Morphometry (VBM) are now published every year and a number of different automated processing pipelines are used, although it remains to be systematically assessed whether they come up with the same answers. Here we examined variability between four commonly used VBM pipelines in two large brain structural datasets. Spatial similarity and between-pipeline reproducibility of the processed gray matter brain maps were generally low between pipelines. Examination of sex-differences and age-related changes revealed considerable differences between the pipelines in terms of the specific regions identified. Machine learning-based multivariate analyses allowed accurate predictions of sex and age, however accuracy differed between pipelines. Our findings suggest that the choice of pipeline alone leads to considerable variability in brain structural markers which poses a serious challenge for reproducibility and interpretation.