OBJECTIVE We examined brain diffusion changes of patients with acromegaly. We searched whether there are differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values between remission and non-remission patients with acromegaly and investigated any effect of time of hormone exposure on diffusion metrics. METHODS The values of FA and ADC were calculated in a total of 35 patients with acromegaly and 28 control subjects. Patients were subdivided into remission and non-remission groups. We looked at brain FA and ADC differences among the groups and looked for any relation between the diffusion changes and time of hormone exposure among the patients with acromegaly. RESULTS We found decreased FA and increased ADC values in some of the growth hormone responsive areas. There were no significant brain diffusion changes between remission and non-remission groups. The most affected areas were the hypothalamus, parietal white matter and pre-motor cortex in patients with acromegaly. In terms of hormone exposure time among the patients with acromegaly, there was no effect of disease duration on brain microstructural changes. CONCLUSIONS All patients with acromegaly showed increased brain diffusion with no relation to disease duration and treatment status. We suggested that in patients with acromegaly, brain damage had already occurred in the subclinical period before symptom onset. CONCLUSIONS This study contributes to the understanding of the mechanisms in acromegaly.