To review literature about risk factors of neonatal hypoxic-ischemic encephalopathy (HIE).Search in PubMed, MEDLINE, Embase, Clinicaltrials.gov and reference lists from 1999 to 2018.study population composed of neonates who manifested HIE within 28 days from delivery, data reported as proportional rate. Studies were excluded if they included preterm pregnancies, postnatal conditions leading to HIE and/or fetal malformations, focused on a single risk factor, were not in English language. PRISMA guidelines were followed. Interstudies heterogeneity was assessed and a random/fixed models were generated as appropriate. Comparison between neonates with HIE vs. controls was performed by calculating odds ratio-95% confidence interval (OR-95% CI). Differences were significant if 95% CI did not encompass 1. Twelve articles were included. Fetuses with growth restriction (OR: 2.87; 95% CI: 1.77-4.67), nonreassuring cardiotocography (OR: 6.38; 95% CI: 2.56-15.93), emergency cesarean section (OR: 3.69; 95% CI: 2.75-4.96), meconium (OR: 3.76; 95% CI: 2.58-5.46) and chorioamnionitis (OR: 3.46: 95% CI: 2.07-5.79) were at higher risk of developing HIE. Nulliparity, gestational diabetes, hypertension, oligohydramnios, polyhydramnios, male sex, induction of labor, labor augmentation, premature rupture of membrane, and vacuum delivery were not significantly different.Neonatal HIE has multifactorial origin and its cause is often undetermined and not preventable.PROSPERO (Registration number: CRD42018106563).