Relative ellipsoid zone reflectivity (rEZR) represents a potential biomarker of photoreceptor health on spectral-domain optical coherence tomography (SD-OCT). Because manual quantification of rEZR is laborious and lacks of spatial resolution, automated quantification of the rEZR would be beneficial. The purpose of this study was to evaluate the reliability and reproducibility of an automated rEZR quantification method. The rEZR was acquired using a manual and an automated approach in eyes with age-related macular degeneration (AMD) and healthy controls. The rEZR obtained from both methods was compared and the agreement between the methods and their reproducibility assessed. 8.2%. An expected perfect reproducibility was observed for the automated method, whereas the manual method had a coefficient of repeatability of 6.3 arbitrary units. The automated quantification of rEZR method is reliable and reproducible. Further studies of the rEZR as a novel biomarker for AMD severity and progression are warranted. Automated quantification of SD-OCT-based rEZR allows for its comprehensive and longitudinal characterization evaluating its relevance as an in vivo biomarker of photoreceptor function and its prognostic value for AMD progression.