To investigate the prevalence of color deficits at age 5 1/2 years in preterm children with birth weights of less than 1251 g who participated in the multicenter Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. Two cohorts of CRYO-ROP participants served as subjects: 1055 children who participated in a long-term study of the natural history of ROP at 5 of the 23 CRYO-ROP centers, and 187 children (from all 23 study centers) who had threshold ROP in both eyes and who were randomized to receive cryotherapy in 1 eye. Monocular color vision was tested at age 5 1/2 years, using the Standard Pseudoisochromatic Plates, part 2 (SPP2) for acquired color vision defects. In the Natural History cohort, prevalence of red-green (RG) color deficits was 6.6% for males and 1.0% for females, similar to that of the general adult population. Prevalence of blue-yellow (BY) color deficits was 2.8% for males and 2.2% for females, more than 200 times that in the general adult population. Prevalence of BY deficits was not related to birth weight, gestational age, acute-phase ROP, optic atrophy, or retinal residua of ROP, but was related to visual acuity. In the Threshold ROP cohort, color vision deficits were no more likely in eyes that had received cryotherapy than in control eyes. The results confirm an increased prevalence of BY deficits in children born before term, and provide evidence that the increased prevalence is not related to birth weight, gestational age, or severity of ROP within this group of preterm children. No evidence was found to indicate that cryotherapy increased the rate of color vision deficits in eyes with threshold ROP.