ABSTRACTBACKGROUND AND PURPOSEHuman entorhinal cortex (ERC) connects the temporal neocortex with hippocampus and is essential for memory retrieval and navigation. Markedly, there have been only few quantitative MRI works on the ERC geometric measurements in pediatric and adult healthy subjects across the lifespan. Here, we sought to fill this gap in knowledge by quantifying the ERC thickness in a very large cohort of subjects spanning 9 decades of life.METHODSUsing magnetic resonance imaging data from multiple centers (IXI, MMRR, NKI, OASIS combined with the NIH‐Child Dev database and locally recruited healthy subjects), we analyzed the lifespan trajectory of ERC thickness in 1,660 healthy controls ranging from 2 to 94 years of age.RESULTSThe ERC thickness increased with age, reached a peak at about 44 years, and then decreased with age. ERC thickness is hemispherically rightward‐asymmetric with no gender differences. Mean ERC thickness was found to vary between 2.943 ± .438 mm and 3.525 ± .355 mm across different age populations. Also, more pronounced loss of the ERC thickness in healthy aging men was noticeable.DISCUSSIONOur report with high spatial resolution brain MRI data from 1,660 healthy controls provided important clues about ERC thickness across lifespan. We believe that our report will pave the way for the future studies investigating distinct neural pathologies related with cognitive dysfunctions.