Introduction: The optimization of enteral nutrition is a priority in preterm neonates worldwide. Probiotics are known to improve gut maturity and function in preterm neonates. To our knowledge, previous systematic reviews have not adequately assessed the effects of probiotic supplementation on enteral nutrition in preterm neonates. Objective: We assessed the evidence on effects of probiotics on enteral nutrition in preterm neonates. Design: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation in preterm (gestation ,37 wk) or low-birthweight (birth weight ,2500 g) neonates was conducted. With the use of the Cochrane Neonatal Review Group strategy, we searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Cumulative Index of Nursing and Allied Health Literature databases and proceedings of Pediatric Academic Society meetings in April 2014. Results: A total of 25 RCTs (n = 5895) were included in the review. A meta-analysis (random-effects model) of data from 19 of 25 trials(n = 4527) estimated that the time to full enteral feeds was shorter in the probiotic group (mean difference: 21.54 d; 95% CI: 22.75, 20.32 d; P , 0.00001, I2 = 93%). Other benefits included fewer episodes of feed intolerance, better weight gain and growth velocity, decreased transition time from orogastric to breast feeds, and increased postprandial mesenteric flow. There were no adverse effects of probiotic supplementation. Conclusions: Probiotics reduced the time to full enteral feeds in preterm neonates. Additional research is necessary to assess the optimal dose, duration, and probiotic strain or strains used specifically for facilitating enteral nutrition in this population. © 2014 American Society for Nutrition.