Objective The purpose of this meta-analysis is to investigate the effect of prophylactic caffeine use in the treatment of apnea and other clinical outcomes in very low birth weight infants. Methods We searched PubMed, Embase, Web of Science, Scopus, EBSCO, CNKI, and Cochrane databases for all relevant studies up to May 20, 2022. The meta-analysis was carried out using Stata16.0 and RevMan5.4 software. Results Eleven randomized controlled trials were evaluated, including a total of 4375 very low birth weight infants. The results demonstrated that prophylactic caffeine use was linked with a significantly lower probability of AOP (OR 0.31, 95% CI: 0.19-0.49, p < .001), duration of mechanical ventilation and oxygen therapy when compared to the control group. It also reduced the incidence of BPD (OR 0.62, 95% CI: 0.54-0.71, p < .001), PDA (OR 0.49, 95% CI: 0.30-0.80, p = .005) and ROP (OR 0.76, 95% CI: 0.65-0.90, p = .001), without raising the risk of NEC, IVH and death before hospital discharge (p > .05). Conclusion This meta-analysis confirmed the beneficial effects of prophylactic caffeine in preventing apnea of prematurity and improving clinical outcomes.