Nosocomial infections(NIs) are the most important current challenge faced by neonatal intensive care units (NICUs). Although systematic surveillance is an integral part of all approaches to decreasing NIs, the current methods for recording healthcare-associated infections in our country are grossly inadequate. To determine the prevalence and risk factors for device-associated infections in a tertiary care center in eastern India. This prospective observational study was undertaken in the NICU, Department of Pediatrics, SCB Medical College, Cuttack, and SVPPGIP, Cuttack. Neonates who stayed in the NICU for more than 48 hours and needed one or more devices (e.g. ventilator or CVL) are included in this study. They were observed for nosocomial infections. In this study, we included 630 neonates. A total of 94 neonates were found to have a nosocomial infection. The patient, days were 2516 days. During the period of study, central line days were found to be 173 days and ventilator days, 710. The prevalence of nosocomial infection was found to be 14.9%. Male babies were more likely to have nosocomial sepsis. Staphylococcus aureus was found to be the major organism. Nosocomial infection in NICU graduates who are put on several devices is an important preventable problem. The present study reveals that sepsis (LOS) and pneumonia are major device-associated infections. Staphylococcus aureus is most commonly associated with E. coli and Klebsiella. Their prevention can be achieved by applying strict protocols for sepsis.