Objective To explore the optimal protocol for treating apnea of prematurity by analyzing the effectiveness of different noninvasive assisted ventilation modes combined with caffeine citrate in preterm infants.Methods From October 2019 to August 2022,a total of 90 infants with apnea of prematurity(gestational age≤34 weeks)were chosen as research objects in the Neonatal Intensive Care Unit of the Second Affiliated Hospital of Bengbu Medical College,and the relevant data were retrospectively analyzed.The children were divided into nasal continuous positive airway pressure(NCPAP)combined with caffeine citrate group(44 cases),and noninvasive inter-mittent positive pressure ventilation(NIPPV)sequential NCPAP combined with caffeine citrate group(46 cases)according to the differ-ent treatment protocols adopted in the clinical treatment process.The general clinical data,apnea efficacy,treatment time,and occur-rence of adverse effects between the two groups of prematurity were compared statistically by t-test,x2test,and Mann-Whitney rank sum test.Results The total efficiency of the NIPPV sequential NCPAP combined with caffeine citrate group in treating apnea of prematu-rity was 91.30％,higher than 86.36％in NCPAP combined with caffeine citrate group,and the difference was statistically significant(P＜0.05).Statistically significant differences in failure of non-invasive ventilation and associated treatment time between the two groups(P＜0.05)were observed.The difference between the two groups in the incidence of feeding intolerance and nasal injury was sta-tistically significant(all P＜0.05).Conclusion Early adoption of NIPPV sequential NCPAP ventilation mode can achieve better clinical results,shorten treatment and hospitalization time,and have relatively fewer adverse effects than traditional NCPAP alone in treating apnea of prematurity,which is worthy of clinical promotion.