Abstract. BACKGROUND: Transient tachypnea of the newborn (TTN) is a self- limited increase in the work of breathing in near- and full-term infants; it is attributed to a delay in the clearance of alveolar fluids. Prophylactic antibiotics are usually administered until blood cultures are reported negative for 48 hours. OBJECTIVES: To prospectively compare outcomes of infants presented with classic TTN who were treated with or denied from intravenous antibiotics. METHODS: A prospective cohort study was conducted on all infants admitted with classic TTN. Pre-set diagnostic criteria for classic TTN were applied in order to exclude other cases presenting with respiratory distress. Infants with classic TTN were stratified into two groups based on whether they received or did not receive antibiotics. The decision to administer antibiotics solely depended upon the style of the covering physician at the time of admission to the NICU. The following investigations were obtained from infants of both groups: blood culture, C-reactive protein, complete blood count, blood gas profile and chest X-ray. RESULTS: A total of 15146 full-term infants were delivered during the study period; of them 923 were admitted to the NICU. Classic TTN was diagnosed in 168 infants; of them 106 (63%) received and 62 (37%) did not receive antibiotics. Two infants in the treated group and an infant in the non-treated group had microbiologically confirmed bacteremia. Infants in the treatment group stayed longer in the hospital (72±6 vs. 48±3 hrs). No recorded cases required readmission in either group. CONCLUSIONS:With the application of strict criteria for classic TTN and the close observation in the NICU, the empiric use of antibiotics may be avoidable. Randomized controlled trials are needed to confirm the feasibility and safety of such approach.