Purpose: We aimed to appraise the effects of the use of probiotics on the incidence and severity of NEC and to compare the results of different probiotic preparations in a large population of premature infants admitted to an Australian Level 6B Neonatal Intensive Care Unit (NICU) over a 10-year period. Method: Retrospective review of clinical outcome of preterm babies <32 weeks gestational age over a 10-year period before the use of probiotics (Group A) or receiving 2 different strains of probiotics [L. acidophilus + B. bifidum (Group B) or L. acidophilus + B. infantis + B. bifidum (Group C)]. Data are reported as number of cases (%), mean ±SD and analysed using GraphPad Prism 10. Results: There were 1256 (57% males) babies in Group A, 623 (49.7% males) in Group B and 297 (48.8%) in Group C. Group A had a significant higher gestational age [28.77 ± 2.25 in Group A vs. 28.23 ± 2.26 in Group B vs. 27.82 ± 2.16 in Group C (p<0.0001)] and birth weight (gr) [1290 ± 435.6 in Group A vs. 1134 ± 361.1 in Group B vs. 1033 ± 283.9 in Group C (p<0.0001)]. Total NEC cases were 34 (2.7) in Group A vs. 19 (3.0) in Group B vs. 9 (3.0) in Group C (p = 0.67). Patient requiring surgery for NEC were 26 (76.5) in Group A vs. 14 (73.7) in Group B vs. 7 (77.7) in Group C (p = 0.98). NEC related deaths were 8 (23.5) in Group A vs. 6 (31.5) in group B vs. 0 (0) in Group C (p = 0.3). Conclusion: In our NICU, the use of 2 different probiotics formulations in a population of low gestational age and birth weight neonates is associated with incidence or severity of NEC comparable to higher gestational age and birth weight neonates.