Abstract Background: Hydroxychloroquine (HCQ) is a less toxic metabolite of chloroquine which is used to treat rheumatic diseases such as systemic lupus erythematosus (SLE), rheu-matoid arthritis (RA), juvenile idiopathic arthritis (JIA) and Sjogren's syndrome. It can cause corneal deposits, ciliary body dysfunction, posterior subcapsular lens opacity, and most important, irregularity in the macular pigmentation in the early phase, a ring of macular pigment dropout in the advanced stage, and peripheral bone spicule formation, vascular attenuation, and optic disc pallor in the end stage. The American Academy of Ophthalmology recommendations for screening that were published in 2016 recommended the use of both automated visual field and SD-OCT for routine primary screening. Aim of Study: Detection of possible adverse effects of long term hydroxychloroquine use on corneal endothelium in patients of rheumatological diseases who used the drug for at least three years. Patients and Methods: This study included 30 eyes of 15 patients with rheumatological diseases who used hydroxy-chloroquine for at least 3 years. The control group included 30 eyes of 15 persons with normal healthy corneas. The participants were gathered from Rheumatology and Ophthal-mology Outpatient Clinics of Ain-Shams University Hospital in the period from December 2019 till May 2020. Results: The study assessed 60 eyes by specular micros-copy, 30 eyes of patients of rheumatological diseases repre-senting the study group and 30 eyes of normal healthy indi-viduals representing the control group. The study revealed a highly significant change in coefficient of variation (CV) in patients who used HCQ for at least 3 years. Conclusion: The present study revealed that there was a highly significant change in coefficient of variation (CV) in patients who used HCQ for at least 3 years. The study revealed a new ocular adverse effect of long term use of HCQ on corneal endothelium.