〔Abstract〕Objective To investigate the effect of aminophylline and caffeine citrate on blood oxygen index in premature infants with primary apnea. Methods 84 premature infants with primary apnea admitted to the Second Affiliated Hospital of Luohe Medical College from August 2019 to August 2021 were randomly divided into a control group and an observation group by random number table method. The control group was treated with aminophylline and the observation group was treated with caffeine citrate. The clinical efficacy, blood oxygen index, serum β -endorphin (β-EP) level and medication safety of preterm infants were compared between the two groups. Results The total effective rate in the observation group was 95.24%, higher than 78.57% in the control group, the difference was statistically significant (P < 0.05). There was no significant difference in blood oxygen index between the two groups before treatment (P > 0.05). After treatment, the arterial partial pressure of oxygen (PaO2) and oxygenation index (OI) in the observation group were higher than those in the control group, while the arterial partial pressure of carbon dioxide (PaCO2) was lower than that in the control group, the differences were statistically significant (P < 0.05). Before treatment, there was no significant difference in serum β -EP level between the two groups (P > 0.05). After treatment, the serum β -EP level in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). The total incidence of adverse reactions such as tachycardia, feeding intolerance and electrolyte disorder in the observation group was 7.14%, lower than 23.81% in the control group , and the difference was statistically significant (P < 0.05). Conclusion Caffeine citrate has significant therapeutic effect and high safety in the treatment of premature infants with primary apnea, and its effect on improving blood oxygen index and reducing serum β -EP level is better than that of aminophylline.