whole slide imaging versus microscopy for primary diagnosis in surgical pathology a multicenter blinded randomized noninferiority study of 1992 cases pivotal study most prior studies of primary diagnosis in surgical pathology using whole slide imaging wsi versus microscopy have focused on specific organ systems or included relatively few cases the objective of this study was to demonstrate that wsi is noninferior to microscopy for primary diagnosis in surgical pathology a blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases biopsies and resections including hematoxylin and eosin immunohistochemistry and special stains from 4 institutions using the original signout diagnosis baseline diagnosis as the reference standard cases were scanned converted to wsi and randomized sixteen pathologists interpreted cases by microscopy or wsi followed by a washout period of 4 weeks after which cases were read by the same observers using the other modality major discordances were identified by an adjudication panel and the differences between major discordance rates for both microscopy against the reference standard and wsi against the reference standard were calculated a total of 1992 cases were included resulting in 15925 reads the major discordance rate with the reference standard diagnosis was 49 for wsi and 46 for microscopy the difference between major discordance rates for microscopy and wsi was 04 95 confidence interval 030 to 101 the difference in major discordance rates for wsi and microscopy was highest in endocrine pathology 18 neoplastic kidney pathology 15 urinary bladder pathology 13 and gynecologic pathology 12 detailed analysis of these cases revealed no instances where interpretation by wsi was consistently inaccurate compared with microscopy for multiple observers we conclude that wsi is noninferior to microscopy for primary diagnosis in surgical pathology including biopsies and resections stained with hematoxylin and eosin immunohistochemistry and special stains this conclusion is valid across a wide variety of organ systems and specimen types