BACKGROUND The control of blindness in children is a high priority within the VISION 2020 initiative. To determine the causes of severe visual impairment and blindness in children from Shanghai Blind Children School (SBCS) can provide useful information on childhood blindness in Shanghai. METHODS A cross-sectional investigation of students in SBCS was conducted in May 2010. The World Health Organization/Prevention of Blindness (WHO/PBL) eye examination record system for children with low vision and blindness was used. The results were further compared with the findings of two previous investigation studies conducted in 1986 and 2004, respectively in SBCS. RESULTS Of the 146 children observed, 80 children (54.8%) were blind (best corrected best visual acuity less than 0.05), 27 children (18.5%) had severe visual impairment (best corrected visual acuity less than 0.1 but better than or equal to 0.05), and 34 children (23.3%) had moderate visual impairment (best corrected visual acuity less than 0.3 but better than or equal to 0.1). The major affected anatomic sites in the 107 children with severe visual impairment and blindness (SVI/BL) were retina (47.7%), whole globe (16.8%), optic nerve (13.1%) and lens (9.3%). The leading causes of SVI/BL were retinopathy of prematurity (ROP, 25.2%), followed by retinal dystrophy (15.9%), optic nerve atrophy (9.3%) and microphthalmos (9.3%). The two leading etiologic categories of SVI/BL were perinatal/neonatal (36.4%) and congenital/hereditary groups (29.0%). The leading cause of moderate visual impairment was aphakia after cataract surgery (congenital cataract, 44.1%). Compared with the findings in two previous investigations in SBCS, the proportion of ROP in visual impairing diseases increased, while the proportion of disorders of the lens (cataract and aphakia) significantly decreased. CONCLUSIONS The leading cause of childhood blindness in SBCS nowadays is ROP. It is projected that without improvement in perinatal medical care that ROP will continue to be a major cause of childhood blindness.