PURPOSE To investigate the relationship between postmenstrual age of onset of retinopathy of prematurity (ROP) and the need for treatment, while examining the effects of two different neonatal oxygen saturation protocols on this relationship. METHODS A retrospective chart review was conducted for eligible inborn infants born before and after the institution of a new oxygen protocol adjusting target oxygen saturation from 90%-99% to 85%-93%. Early versus late-onset ROP was defined as first presence of any stage disease on examination at <36 versus ≥ 36 weeks' postmenstrual age, respectively. RESULTS The median birth weight/postmentrual age of infants was 840 g per 26.1 weeks (early-onset ROP) versus 952.5 g per 28 weeks (late-onset ROP; P < 0.01 vs P < 0.01). ROP developed in 119 of 369 (32.2%) of high oxygen target infants, and 100 of 373 (26.8%) infants in the low-target group (P = 0.11). Cumulatively, 35 of 144 (24.3%) of early-onset and 8 of 69 (11.6%) of late-onset patients required treatment (P = 0.03). Maximal severity of disease after treatment, including retinal detachment frequency, was similar in early- and late-onset patients, independent of the oxygen protocol (P = 1.00). CONCLUSIONS The clinical behavior of type 1 ROP is similar in early-and late-onset disease, regardless of oxygen saturation targets. Type 1 ROP disease occurred in 11.6% of patients with late-onset ROP.