Abstract : Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality in preterm neonates, necessitating the exploration of novel preventive strategies. Azithromycin, with its anti-inflammatory and antimicrobial properties, has shown potential in this context. This study systematically evaluates the effectiveness and safety of azithromycin in preventing BPD in preterm neonates. Following PRISMA guidelines, Medline, Cochrane, and Embase databases were searched for studies assessing azithromycin therapy in preterm infants, with BPD as the primary outcome and safety as the secondary outcome. Two reviewers independently screened studies, extracted data, and assessed bias using the Cochrane Risk-of-Bias Tool and MINORS scale. A fixed-effect model was applied to compute pooled risk ratios (RRs) with 95% confidence intervals (CIs), complemented by subgroup analyses. Ten studies involving 1,523 preterm neonates were included. Meta-analysis revealed no significant difference in the incidence of BPD (RR 1.00, 95% CI 0.94–1.06), death before discharge (RR 0.84, 95% CI 0.64–1.11), death after discharge (RR 1.03, 95% CI 0.42–2.55), or respiratory morbidity (RR 0.96, 95% CI 0.54–1.69). However, in the ureaplasma-negative subgroup, azithromycin significantly reduced the risk of death before discharge (RR 0.58, 95% CI 0.38–0.89). No studies reported pyloric stenosis or QT prolongation, and neurodevelopmental outcomes showed no significant difference. In conclusion, azithromycin therapy is safe but ineffective in reducing the risk of BPD in preterm neonates. These findings emphasize the need for multifaceted therapeutic approaches to address the complex, multifactorial nature of this disease.