This proposal requests support for Thomas Jefferson University Hospital as a Participating Center in the Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) Study. The application documents this center's ability to recruit a projected 15 eligible infants per year. This center will participate with the Study Headquarters in Rochester, New York and the Coordinating Center at The EMMES Corporation in Maryland, and will comply with the study design and Manual of Operations which will be submitted separately by the Headquarters and Coordinating Center. Retinopathy of Prematurity (ROP) remains a serious public health problem causing significant visual sequelae in an estimated 3400 premature infant survivors per year in the United States, despite the accepted use of Cryotherapy. Case control studies in premature infants, anecdotal reports of successful treatment of ROP with oxygen, and studies conducted in experimental models demonstrate that chronic (weeks-long) hypoxia during the healing process is associated with retinopathy that progresses rather than regresses. This hypothesis is also supported by the association of proliferative retinopathies with retinal ischemia in other disorders such as diabetic or sickle cell retinopathies. Therefore, we proposed to test the hypothesis that "Supplemental Oxygen Treatment of Prethreshold ROP will result in a reduction by at least one third in the number of infants with one or both eyes progressing to severe ROP (Threshold)." Infants who develop moderate ROP (Prethreshold as defined in the CRYO-ROP study) will receive continuous pulse oximetry saturation monitoring and be randomly assigned to oxygen administration at one of two specified oxygen levels: conventional vs supplemental. Their ROP status will be measured and recorded prospectively, and the primary outcome variable will be the proportion of infants who progress to Threshold ROP in at least one eye. Followup will continue to three months following the projected time of full term delivery. The projected sample sizes are compatible with a 2-3 year enrollment with 20-30 participating centers. Should this approach prove effective, the additional oxygen is also expected to benefit these infants through the reduction of cor pulmonale associated with bronchopulmonary dysplasia often observed in these infants.