Purpose To investigate causes of childhood blindness in the United States using the IRIS® Registry (Intelligent Research in Sight). Design Cross-sectional study. Participants Patients ≤ 18 years of age with visual acuity (VA) 20/200 or worse in their better-seeing eye in the IRIS Registry during 2018. Methods Causes of blindness were classified by anatomic site and specific diagnoses. Main Outcome Measures Percentages of causes of blindness. Results Of 81 164 children with 2018 VA data in the IRIS Registry, 961 (1.18%) had VA 20/200 or worse in their better-seeing eye. Leading causes of blindness were retinopathy of prematurity (ROP) in 301 patients (31.3%), nystagmus in 78 patients (8.1%), and cataract in 64 patients (6.7%). The retina was the leading anatomic site (47.7%) followed by optic nerve (11.6%) and lens (10.0%). A total of 52.4% of patients had treatable causes of blindness. Conclusions This analysis offers a unique cross-sectional view of childhood blindness in the United States using a clinical data registry. More than one-half of blind patients had a treatable cause of blindness. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. To investigate causes of childhood blindness in the United States using the IRIS® Registry (Intelligent Research in Sight). Cross-sectional study. Patients ≤ 18 years of age with visual acuity (VA) 20/200 or worse in their better-seeing eye in the IRIS Registry during 2018. Causes of blindness were classified by anatomic site and specific diagnoses. Percentages of causes of blindness. Of 81 164 children with 2018 VA data in the IRIS Registry, 961 (1.18%) had VA 20/200 or worse in their better-seeing eye. Leading causes of blindness were retinopathy of prematurity (ROP) in 301 patients (31.3%), nystagmus in 78 patients (8.1%), and cataract in 64 patients (6.7%). The retina was the leading anatomic site (47.7%) followed by optic nerve (11.6%) and lens (10.0%). A total of 52.4% of patients had treatable causes of blindness. This analysis offers a unique cross-sectional view of childhood blindness in the United States using a clinical data registry. More than one-half of blind patients had a treatable cause of blindness.