Perinatal hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological sequelae in later life. The aim of our study is to identify the factors that are associated with a higher degree of severity in HIE and evaluate the outcomes. We performed a retrospective study of all newborns with HIE treated at our neonatal intensive care unit (NICU) from January 2010 to December 2013. Data collected include information about prenatal period, peripartum period, demographic characteristics, admission and evolution during NICU stay and outcomes (assessed in three different times: at discharge, at 6-9 months and 18 months). Forty seven newborns were enrolled in our study, 11 (23.4%) with mild HIE, 21 (44.7%) with moderate HIE and 15 (31.9%) with severe HIE. Prenatal, perinatal and demographic data showed no statistically significant differences between groups. Statistically significant differences were found in values of Thompson score (p < 0.0001), abnormal aEEG/EEG at admission (p = 0.025) and at 48 hours (p = 0.018), need of mechanical ventilation (p = 0.004), acute renal failure (p = 0.002) and length of stay (p = 0.038) with high rates in the moderate and severe HIE groups. Regarding the outcomes, statistically significant differences were found in the prevalence of death (p = 0.010); need of antiepileptic drugs at discharge (p = 0.001); motor deficits requiring physiotherapy (p = 0.046), abnormal deep tendon reflex (p = 0.006) and need of antiepileptic drugs (p = 0.001) at 6-9 months follow-up; and cerebral palsy with cognitive impairment at 18 months (p = 0.041) with high rates in the severe HIE group. These results suggest that Thompson score, abnormal aEEG/EEG at admission and at 48 hours, mechanical ventilation, acute renal failure and length of stay are associated with more severe HIE. We also concluded that more severe HIE reflects worse outcomes whereas mild HIE is associated with normal outcome in the majority of patients at 18 months.