A number of MRI methods have been proposed to be useful, quantitative biomarkers of neurodegeneration in ageing. The Calgary Normative Study (CNS) is an ongoing single-centre, prospective, longitudinal study that seeks to develop, test and assess quantitative magnetic resonance (MR) methods as potential biomarkers of neurodegeneration. The CNS has three objectives: first and foremost, to evaluate and characterise the dependence of the selected quantitative neuroimaging biomarkers on age over the adult lifespan; second, to evaluate the precision, variability and repeatability of quantitative neuroimaging biomarkers as part of biomarker validation providing proof-of-concept and proof-of-principle; and third, provide a shared repository of normative data for comparison to various disease cohorts. Quantitative MR mapping of the brain including longitudinal relaxation time (T1), transverse relaxation time (T2), T2*, magnetic susceptibility (QSM), diffusion and perfusion measurements, as well as morphological assessments are performed. The Montreal Cognitive Assessment (MoCA) and a brief, self-report medical history will be collected. Mixed regression models will be used to characterise changes in quantitative MR biomarker measures over the adult lifespan. In this report, we describe the study design, strategies to recruit and perform changes to the acquisition protocol from inception to 31 December 2018, planned statistical approach and data sharing procedures for the study. Participants provide signed informed consent. Changes in quantitative MR biomarkers measured over the adult lifespan as well as estimates of measurement variance and repeatability will be disseminated through peer-reviewed scientific publication. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.