Purpose To longitudinally evaluate the cortical thickness and deep gray matter structures volume, measured from T1 three‐dimensional (3D) Gradient echo‐weighted imaging, and white matter integrity, assessed from diffusion tensor imaging (DTI) of HIV‐positive patients. Materials and Methods Twenty‐one HIV‐positive patients on stable highly active antiretroviral therapy (HAART) with CD4+ T lymphocytes count >200 cells/mL and viral load <50 copies/mL underwent two magnetic resonance imaging (MRI) scans with a median interval of 26.6 months. None of the patients had HIV‐related dementia. T1 3D magnetization prepared rapid gradient echo‐weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5 Tesla MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract‐based spatial statistics analysis, a white matter skeleton was created, and a permutation‐based inference with 5000 permutations, with a threshold of P < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The median, radial, and axial diffusivities were also projected onto the mean FA skeleton. Results There were no significant differences in cortical thickness, deep gray matter structures volumes or diffusivity parameters between scans at the two time points (considering P < 0.05). Conclusion No longitudinal differences in cortical thickness, deep gray matter volumes, or white matter integrity were observed in an HIV‐positive population on stable HAART, with undetectable viral load and high CD4+ T lymphocytes count. J. Magn. Reson. Imaging 2016;44:1262–1269.