© 2018 American Medical Association. All rights reserved. IMPORTANCE There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. OBJECTIVE To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (SpO2) on death or major morbidity. DESIGN, SETTING, AND PARTICIPANTS Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks’ gestation. EXPOSURES SpO2 target range that was lower (85%-89%) vs higher (91%-95%). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as 2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. RESULTS A total of 4965 infants were randomized (2480 to the lower SpO2 target range and 2485 to the higher SpO2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower SpO2 target group and 1150 of 2229 infants (51.6%) in the higher SpO2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower SpO2 target group, and 3 significantly favored the higher SpO2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower SpO2 target group and 418 of 2440 infants (17.1%) in the higher SpO2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower SpO2 target group and 308 of 2065 infants (14.9%) in the higher SpO2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower SpO2 target group and 170 of 2465 infants (6.9%) in the higher SpO2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). CONCLUSIONS AND RELEVANCE In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower SpO2 target range compared with a higher SpO2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower SpO2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.