Background: There has been a shift towards early initiation of caffeine citrate, while the efficacy and safety of prophylactic use and higher dosing of caffeine is still not well established. Objectives: The aim of this study is to find the efficacy of early high-dose caffeine (HD) therapy on significant apnea, duration of invasive or non-invasive ventilation and short outcomes in preterm infants admitted in Intensive Care Unit (NICU) at Al-Hussein University Hospital.  Patients & Methods: This prospective observational study was conducted during the period from January 2023 to December 2023 on 50 preterm admitted to NICU. They were divided into two groups: Group 1 included 25 preterm who received high maintenance dose of caffeine citrate 10 mg/kg/day intravenous with loading dose 20 mg/kg/day given less than 24h of life, and Group 2 include 25 preterm who received low maintenance dose of caffeine citrate 6 mg/kg/day intravenous with variable timing of loading dose 20 mg/kg/day. The Caffeine treatment lasted up to 34–35 wk of Postmenstrual age. Complete clinical examination, history taking and laboratory investigation was done at time of admition.   Results:  The Results showed that the Mean ± SD of Gestational age (weeks) was28.72 ± 1.02 in group 1 and 29.80 ± 0.71 in group 2 ;( 52.0%) Female and (48.0%) male in group 1 where (48.0%) Female and (52.0%) Male in group 2. Also, There was statistically significant difference between studied groups as regard duration of MV with significant increase in duration of oxygen therapy in group2 than group1. Duration of hospital stay was significant long in group2 than group1. As regard developing of bronchopulmonary dysplasia (BPD) there was significant increase in group2 (15 cases = 60%) than group1 (7 cases = 28%). Conclusion:  The study revealed that the initiating caffeine citrate therapy within the first day of life in heigh dose ( ≥10 mg/kg/day) was associated with marked decreased duration of MV and apnea recurrence than that observed in infants with low dose ( ≤ 6 mg/kg/day) initiation with a statistically significant reduction in the rates of morbidity. Further studies should be done to determine optimal dose and duration of caffeine therapy and the long-term outcomes in preterm infants.