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Introduction: Caffeine is one of the most used drugs in the neonatal intensive care units (NICUs). It is widely regarded as beneficial in preventing many morbidities by reducing apnea of prematurity and improving respiratory functions., Methods: Premature infants with gestational ages >25 and <32 weeks who were hospitalized in the NICU between 2008 and 2013 and survived up to discharge were retrospectively analyzed. Infants treated with prophylactic caffeine were compared with historical controls born in 2008 and did not receive caffeine treatment. Maternal and neonatal characteristics and common neonatal morbidities were recorded., Results: A total of 475 patients were analyzed. The patients receiving caffeine were classified as Group 1 ( n  = 355), and the patients not receiving caffeine were classified as Group 2 ( n  = 120). Despite the higher incidence of respiratory distress syndrome requiring surfactant therapy and a longer duration of respiratory support in Group 2, the rates of bronchopulmonary dysplasia (BPD) and most other common morbidities were quite comparable. The frequency of apnea was statistically lower in the group that received caffeine prophylaxis ( p  < 0.01)., Conclusion: In this retrospective cohort analysis, we found that caffeine prophylaxis significantly decreased apnea attacks however does not prevent respiratory morbidity such as BPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yavanoglu Atay, Kanmaz Kutman, Bidev, Bozkurt Kalyoncu and Oğuz.)