ABSTRACT: Importance:Evaluating prefeed gastric residuals is considered routine care but has little supporting evidence. Objective:To determine the effect of omitting prefeed gastric residual evaluation on nutritional outcomes in extremely preterm infants. Design, Setting, and Participants:This single-center randomized clinical trial compared the omission of gastric residual evaluation with prefeed gastric residual evaluation. Infants were recruited from a level 4 neonatal intensive care unit and were enrolled from October 17, 2013, to October 8, 2016, and then followed up for 6 weeks after birth. Eligible participants were infants born at 32 or fewer weeks' gestation with a birth weight of 1250 g or less; they were enrolled within 72 hours after birth and within 24 hours after feeding initiation. All participants (N?=?143) were included in the modified intent-to-treat analysis, which was conducted from March to July 2018. Interventions:The residual group underwent prefeed gastric residual evaluation; the no residual group did not. Feeding decisions were made according to nutritional guidelines, and infants received only human milk. Main Outcomes and Measures:The primary outcome was weekly enteral nutrition intake in mL/kg for 6 weeks after birth. Results:Of 143 infants, 74 (51.7%) were randomized to undergo gastric residual evaluation (residual group) and 69 (48.3%) to omitted gastric residual evaluation (no residual group). The residual group comprised an even number of male and female infants (37 [50.0%]) with a mean (SD) gestational age of 27.1 (2.4) weeks and a mean (SD) birth weight of 888.8 (206.6) grams, whereas the no residual group had more male infants (36 [52.17%]), a mean (SD) gestational age of 27 (1.2) weeks, and a mean (SD) birth weight of 915.2 (180) grams. The no residual group had feedings that advanced more quickly compared with the residual group (mean weekly increase, 20.7 mL/kg/d vs 17.9 mL/kg/d; P?=?.02) and consumed more feedings at weeks 5 (137.2 [95% CI, 128.6-145.8]; P?=?.03) and 6 (141.6 [95% CI, 133.2-150.0]; P?=?.03). Among the secondary outcomes, the no residual group had higher mean estimated log weights (7.01 [95% CI, 6.99-7.02] vs 6.98 [95% CI, 6.97-7.00]; P?=?.03), had fewer episodes of abdominal distention (0.59 [95% CI, 0.34-1.01] vs 1.79 [95% CI, 1.27-2.53]; P?=?.001), and were discharged 8 days earlier (4.21 [95% CI, 4.14-4.28] vs 4.28 [95% CI, 4.19-4.36]; P?=?.01). Odds for necrotizing enterocolitis (0.058 [95% CI, 0.018-0.190] vs 0.026 [95% CI, 0.006-0.109]), death (0.004 [95% CI, 0.0003-0.046] vs 0.012 [95% CI, 0.001-0.131]), late-onset sepsis (0.970 [95% CI, 0.67-1.40] vs 1.38 [95% CI, 0.97-1.94]), and ventilator-associated pneumonia (0.084 [95% CI, 0.033-0.214] vs 0.056 [95% CI, 0.019-0.168]) were similar between groups. Conclusions and Relevance:Among extremely preterm infants, the omission of gastric residual evaluation increased the delivery of enteral nutrition as well as improved weight gain and led to earlier hospital discharge; these results may translate into evidence-based practice. Trial Registration:ClinicalTrials.gov identifier: NCT01863043.