The effect of probiotics on late-onset sepsis (LOS) in preterm neonates remains controversial. The authors systematically reviewed the literature to investigate whether enteral probiotic supplementation reduced the risk of LOS in preterm neonates in neonatal intensive care units.PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) regarding the effect of probiotics in preterm neonates. The primary outcome was culture-proven bacterial and/or fungal sepsis. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs).Twenty-seven trials were included in our review, and 25 trials involving 6104 preterm neonates were statistically analyzed. Pooled analysis indicated that enteral probiotic supplementation significantly reduced the risk of any sepsis (25 RCTs; RR 0.83, 95% CI 0.73-0.94; I = 26%), bacterial sepsis (11 RCTs; RR 0.82, 95% CI 0.71-0.95; I = 0%), and fungal sepsis (6 RCTs; RR 0.57, 95% CI 0.41-0.78; I = 0%). This beneficial effect remains in very low birth weight infants (