PURPOSE: To analyze the retinal imaging findings and natural history of Best vitelliform macular dystrophy (BVMD). DESIGN: Single-center retrospective, consecutive, observational study. PARTICIPANTS: Patients with a clinical diagnosis of BVMD, from pedigrees with a likely disease-causing monoallelic variant in BEST1. METHODS: Data were extracted from electronic and physical case notes. Retinal imaging with optical coherence tomography (OCT) and fundus autofluorescence (FAF) was analyzed cross-sectionally and longitudinally. MAIN OUTCOME MEASUREMENTS: Qualitative and quantitative OCT and FAF analysis. RESULTS: 222 patients (127 males and 95 females) from 141 families were included. Mean central retinal thickness on OCT at baseline was 337.2 μm for the right eye and 341.1 μm for the left eye, with a mean annual thickness loss of 5.7 μm and 5.2 μm respectively. The presence of the OCT features: pre-vitelliform lesion, solid vitelliform lesion, vitelliform lesion with subretinal fluid and focal choroidal excavation were associated with a better mean visual acuity (VA), whereas the presence of intraretinal fluid and atrophy/fibrosis were correlated with a worse mean VA. FAF showed an area of hyperautofluorescence at the posterior pole in 138 eyes (34.7%), a circumscribed area of hyperautofluorescence superior or superotemporal of the optic nerve head in 53 eyes (13.3%), fibrotic changes in 48 eyes (12.1%) and atrophy in 41 eyes (10.3%). CONCLUSIONS: BVMD shows a wide spectrum of phenotypes on OCT and FAF imaging. The slow and variable disease course may pose a challenge in identification of early endpoints for therapeutic trials aimed at altering kinetics of degeneration.