Abstract: Objective To investigate the efficacy of caffeine citrate and aminophylline in the treatment of apnea in preterm infants and its effect on the development of cranial nerves. Methods From January 2015 to December 2016, 156 cases of apnea premature infants in our hospital were selected as the research object, and were randomly divided into the observation group with 78 cases and the control group with 78 cases. The observation group was treated with citrate caffeine on the basis of routine treatment, and the control group was treated with aminophylline on the basis of routine treatment. The clinical efficacy, complications and cranial nerve development were compared between the two groups. Results The total effective rate was 84.6% in the observation group and 79.5% in the control group. There was no significant difference in the total effective rate between the observation group and the control group (P>0.05); The rate of heart rate increasing, hyperglycemia, feeding intolerance, bronchopulmonary dysplasia and electrolyte disturbance in the observation group were lower than those in the control group, the difference was statistically significant (P<0.05); Before treatment, there was no significant difference in MDI and PDI scores between the two groups (P>0.05). After treatment, the scores of MDI and PDI in the two groups were higher than before treatment, and the observation group was higher than that of the control group, the difference was statistically significant (P<0.05); Before treatment, there was no significant difference in Gesell scores between the two groups (P>0.05). After treatment, the scores of Gesell scores in the two groups were higher than before treatment, and the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). Conclusion Caffeine citrate and aminophylline can effectively treat apnea in preterm infants, but caffeine citrate is safer, and can significantly improve the development of cranial nerves.