Background: Pan-resistant Acinetobacter infection has emerged as an important nosocomial pathogen in our inPatient neonates over the past few years. Methodology: We performed a retrospective chart review during a five-year period (July 2003 - June 2008) of all neonates hospitalized in our neonatal intensive care unit (NICU) who developed Acinetobacter infection to identify mortality-associated risk factors in Acinetobacter neonatal infection. Results: During the five-year study period, 122 cultures from 78 neonates grew Acinetobacter. Source sites of positive culture were in the following descending order: blood (n = 57), trachea (n = 55), tissue/wound/body fluids (n = 4), eye (n = 4), urine (n = 1), and cerebrospinal fluid (n = 1). Twenty-four (31%) Patients had Acinetobacter isolated from more than one site. At the time of admission the mean age was 2.08 +/- 4 days and mean weight was 1.77 +/- 0.88 kg, 75% were premature. Pan-resistance (87/122, sensitive only to Polymyxin) was present in 71% of Acinetobacter isolates. Crude mortality rate of this cohort was 47%, while 70% of Patients died within four days after positive Acinetobacter culture. We identified weight of less than 1 kg on admission (p 0.06, adjusted Odds Ratio (AOR) 1.53), gestational age 28 weeks or less (p 0.011, AOR 2.88), poor perfusion (p 0.007, AOR 2.4), thrombocytopenia (p 0.01, AOR 1.6) and metabolic acidosis (p 0.01, AOR 1.67) as predictors associated with poor outcome. Conclusion: Pan-resistant Acinetobacter infection is exceedingly fatal in newborns, particularly in premature and very low-birth weight neonates. Rational antibiotic use and vigilant infection control in NICUs are key to controlling multi-drug resistant Acinetobacter infection and improving clinical outcome