Objective: The purpose of this meta-analysis is to investigate the effect of prophylactic caffeine use in the treatment of apnea and other clinic outcomes in very low birth weight infants. Methods: From inception to 20 May 2022, PubMed, Embase, Web of Science, Scopus, EBSCO, CNKI, and Cochrane databases were systematically searched. The meta-analysis was carried out using STATA and RevMan software. Results: Eleven randomized controlled trials including a total of 4375 very low birth weight infants were evaluated. The pooled demonstrated that prophylactic caffeine use was linked with a significantly lower probability of AOP (OR 0.31, 95%CI: 0.19-0.49, P<0.001), duration of mechanical ventilation, and oxygen therapy when compared to control group. It also reduced the incidence of BPD (OR 0.62, 95%CI: 0.54-0.71, P<0.001), PDA (OR 0.49, 95%CI: 0.30-0.80, P=0.005) and ROP (OR 0.76, 95%CI: 0.65-0.90, P=0.001), without raising the risk of NEC, IVH and death before hospital discharge ( P＞0.05). Conclusion: This meta-analysis confirmed the beneficial effects of prophylactic caffeine for preventing apnea of prematurity as well as for improving clinical outcomes. However, further research is needed before recommending widespread use of caffeine as a prophylactic treatment in the management of all preterm infants.