Objective To compare the effects of caffeine citrate and aminophylline combined with naloxone in the treatment of premature infants with apnea. Methods From March 2015 to March 2017, 140 premature infants with apnea who were treated in neonatal intensive care unit in Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou were selected in the research.The children were randomly divided into the study group and the control group according to the digital table, with 70 cases in each group.The control group was treated with aminophylline combined with naloxone, and the observation group was treated with caffeine citrate.The adverse reaction of children during the treatment was recorded, and the level of apnea was evaluated after treatment.The blood gas index of children before and after 48h treatment was compared, the mortality rate of the children was counted, and the incidence of brain injury during the 1 year follow-up was analyzed. Results After treatment for 48h, the level of PaO2 in the two groups was significantly higher[study group: (10.54±0.41) kPa, control group: (9.66±0.39) kPa] than those before treatment[study group: (7.18±0.26) kPa, control group: (7.21±0.24) kPa], and the level of PaCO2[study group: (5.31±0.24) kPa, control group: (5.82±0.25) kPa]was significantly lower than those before treatment[study group: (6.83±0.28) kPa, control group: (6.77±0.30) kPa](t=19.153, 13.624, 11.271, 7.304; P=0.000, 0.000, 0.000, 0.000), and the level of PaO2 in the study group was significantly higher than that in the control group, and the level of PaCO2 in the study group was significantly lower than that in the control group(t=6.029, 4.327; P=0.000, 0.000). The overall effective rate of apnea therapy in the study group(92.86%) was significantly higher than 77.14% in the control group (χ2=4.509, P=0.034). The mortality rate(1.43%) and the incidence rate of brain injury(0.00%) of the study group were significantly lower than those of the control group(10.00% and 7.14%)(χ2=4.773, 5.185; P=0.029, 0.023). The incidence rate of adverse reactions(30.00%) of the study group was significantly lower than 50.00% of the control group (χ2=5.833, P=0.016). The endometrial thickness of the study group was significantly lower than that of the control group(P<0.05). The rate of ovulation success(87.84%) and pregnancy success rate(45.94%) of the study group were significantly higher than those of the control group(72.97% and 28.39%)(χ2=5.189, 4.890; P=0.023, 0.027). The rate of abortion(8.82%) of the study group was significantly lower than 33.33% of the control group (χ2=5.242, P=0.022). During the period of treatment, the incidence rate of adverse drug reactions(6.77%) of the study group was not significantly different from 8.11% of the control group (χ2=0.098, P=0.754). Conclusion Compared with aminophylline combined with naloxone treatment, caffeine citrate can significantly improve the blood gas status of apnea preterm infants, improve the overall curative effect of apnea, prevent the occurrence of neonatal death and brain injury, and reduce the adverse reactions of the children during the treatment.It is worthy of clinical application. Key words: Infant, premature, diseases; Apnea; Caffeine citrate; Aminophylline; Naloxone; Comparative effectiveness research