Objective To analyze the therapeutic effects of Caffeine citrate and Aminophylline on pulmonary function, serum insulinlike growth factor binding protein-3 (IGFBP-3) and β- Endorphins(β-EP) levels in premature infants with apnea of prematurity (AOP). Methods A total of 70 cases premature infants with AOP who were admitted to Huiyang Sanhe Hospital from March 2020 to May 2021 were selected as the research objects. According to the random number table, they were divided into the control group (35 cases, treated with Aminophylline injection) and the observation group (35 cases, treated with Caffeine citrate), premature infants in the two groups were treated for 7 d continuously. The clinical efficacy, pulmonary function indexes, serum IGFBP-3 and β-EP levels before and after treatment, and the occurrence of complications during treatment of premature infants between the two groups were compared. Results The total clinical effective rate of premature infants in the observation group was significantly higher than that in the control group (P 0.05); the levels of minute ventilation (MV), tidal volume (VT), peak time ratio (tptef/TE), peak volume ratio (VPEF/VE), respiratory ratio (TI/TE) and serum IGFBP-3 increased significantly after treatment, and the observation group was significantly higher than the control group; while the level of serum β-EP reduced significantly after treatment, and the observation group were significantly lower than the control group (all P