Necrotising enterocolitis (NEC) is a significant cause of infant morbidity and mortality, disproportionately affecting those of extreme prematurity and/or very low birth weight. A number of risk factors have been identified, including an association between the use of antibiotics, and the subsequent development of NEC. This review sought to address whether the choice of antibiotic(s) used to treat infants with suspected late-onset sepsis (LOS) influences the risk of developing NEC. A systematic review was performed across Web of Knowledge, Cochrane Library, Ovid Medline, EMBASE and CINAHL databases, up to February 2018, assessing the primary outcome of NEC occurrence, as extracted directly from the published articles. Studies were included if they were randomised control trials (or featured adequate adjustment for confounders); included clear criteria for defining LOS/NEC; and assessed occurrence of NEC in premature infants treated for LOS with intravenous antibiotics. Studies were excluded if non-original, not exclusively featuring premature infants, or where treatment was given for early-onset sepsis only. 2291 titles and abstracts were identified, of which one study (81 subjects) was suitable for analysis, following screening against eligibility criteria. This suggested a decreased risk of developing definite NEC following treatment with a vancomycin/aztreonam combination, versus a vancomycin/gentamicin regimen (OR = 0·08, 95%CI = 0·00-1·45). This systematic review identified one study where the occurrence of NEC was reported in the context of comparing different antibiotic regimens for late onset sepsis and highlights that the type of antibiotic used to treat LOS in preterm infants might be a determinant of the risk of developing NEC. Although it is known that different antibiotic combinations impact the enteric microbiome and that antibiotic exposure is a risk factor for NEC, there is a paucity of well-designed studies that look at the relationship between NEC risk and specific antibiotic exposures.