Background <p>Previous studies have suggested that probiotics may have potential benefits for preterm infants. Their efficacy seems to depend on the particular species or combinations used.</p> Methods <p>To further investigate the effects of probiotics in preventing necrotizing enterocolitis (NEC) and other related outcomes in preterm infants, we conducted a network meta-analysis of 51 randomized controlled trials involving 11,661 participants.</p> Results <p>Our study revealed that most probiotics can effectively reduce the incidence of NEC (at or beyond Bell’s stage II). Lactobacillus (RR, 0.59; 95% CI: 0.29, 0.98), the combination of Bifidobacterium and Lactobacillus (RR, 0.47; 95% CI: 0.20, 0.87), and the combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR, 0.17; 95% CI: 0.00, 0.84) were the only treatments that significantly reduced all-cause mortality compared to placebo. Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81) and reaching full enteral feeding (MD, -2.15; 95% CI: -3.70, -0.64).</p> Conclusions <p>The combination of Bifidobacterium, Lactobacillus, and Enterococcus was the most efficacious in reducing the mortality and incidence of NEC (Bell II or above) in preterm infants. Both prebiotics and Lactobacillus alone were found to be highly effective in reducing the length of hospitalization and the time needed to achieve full enteral feeding. No evidence suggests that probiotics affect sepsis risk.</p> Trial registration <p>The study protocol was registered with PROSPERO (CRD42023460231) on March 10, 2023.</p>