Anisometropia is a common cause of amblyopia. The relationship between anisometropia, patient age, and the development of amblyopia is unknown. Photoscreening identifies children with anisometropia in a manner that is not biased by visual acuity and allows a unique opportunity to evaluate how patient age influences the prevalence and depth of anisometropic amblyopia. A statewide preschool photoscreening program screened 120,000 children and identified 792 with anisometropia greater than 1.0 diopter. Age was correlated with visual acuity and amblyopia depth. Data were compared with those from 562 strabismic children similarly identified. Only 14% (6/44) of anisometropic children aged 1 year or less had amblyopia. Prevalence was 40% (32/80) for 2-year-olds, 65% (119/182) for 3-year-olds, and peaked at 76% (age 5). Amblyopia depth also increased with age. Moderate amblyopia prevalence was 2% (ages 0 to 1), 17% (age 2), and rose steadily to 45% (ages 6 to 7). Severe amblyopia was rare prior to age 4, 9% at age 4, 14% at age 5, and 9% at ages 6 to 7. In contrast, children with strabismus had a stable prevalence of amblyopia (30% at ages 0 to 2, 42% at ages 3 to 4, 44% at ages 5 to 7). Younger children with anisometropic refractive error have a lower prevalence and depth of amblyopia than do older children. By age 4, when most children undergo traditional screening, amblyopia has usually already developed. New vision screening technologies that allow early detection of anisometropia provide ophthalmologists an opportunity to intervene early, perhaps retarding, or even preventing, the development of amblyopia.