The present study was conducted to investigate the clinical significance of caffeine and aminophylline in the treatment of premature infants with apnea under varying conditions of oxygen (O 2) delivery. The clinical data of 120 premature infants with apnea treated with oxygen therapy and either caffeine citrate (20 mg/kg/day; n=77) or aminophylline (10 mg/kg/day; n=43) were retrospectively examined. The therapeutic performance of the drugs after the completion of the treatment was evaluated primarily according to the risk of recurrent episodes of apnea, the changes in the duration and concentration of inhaled O 2 and the incidence of complications. In contrast to aminophylline, caffeine treatment significantly reduced the duration of O 2 inhalation and the inhaled O 2 concentration in the infants treated with mechanical ventilation or O 2 delivery devices (P<0.05). Treatment with caffeine also decreased the incidence of recurrent apnea events and complications in the investigated population (P<0.05 or P<0.01). Caffeine performs better than aminophylline in the treatment of premature infants with apnea under different conditions of O 2 delivery. The therapeutic performance of caffeine is achieved primarily via improving the efficacy of supplemental O 2 and reducing the incidence of complications.