Objective: Identify perinatal risk factors for transient tachypnea and pneumonia in neonates, and compare the outcome of these clinical conditions during the Neonatal Intensive Care Unit (NICU) stay. Methods: Retrospective review of newborns admitted to a level III NICU, comparing patients with transient tachypnea, pneumonia and a control group of healthy neonates. Results: We included 202 patients with transient tachypnea, 29 with pneumonia and 498 controls. Perinatal infectious risk factors were more frequent in patients with pneumonia than in transient tachypnea (p < 0.001), but the two were identical in terms of the remaining perinatal variables. Patients with pneumonia were admitted for a longer period (p < 0.001) and required supplemental oxygen and ventilatory support more frequently and for a longer period. Comparing with controls, Apgar score at one and five minutes was higher in controls than in patients with pneumonia (p0.032 and p < 0.001) or transient tachypnea (p < 0.001 and p < 0.001). Conclusion: In most cases, newborns with transient tachypnea and pneumonia are indistinguishable at presentation but clinical evolution is significantly different. The presence of perinatal infectious risk supports the diagnosis of pneumonia. Low Apgar score at one and five minutes was associated with both diseases, suggesting that etiologic factors may already be present at birth.