Background: In neonates with meconium aspiration syndrome (MAS), continuous positive airway pressure (CPAP) may be more beneficial compared to endotracheal intubation (ETI). We evaluated the efficacy of CPAP in neonates with MAS. Methods: Four engines were used to search randomized clinical trials (RCTs). We used relative risk (RR) and mean difference (MD) with 95% confidence intervals (95%CI) to assess the effect on dichotomous and continuous outcomes, respectively. In addition, we used the Paule–Mandel (PM) random effects model due to the anticipated lack of events. Results: Three RCTs were included (n = 432). No significant difference was found in mortality (RR = 0.82; 95%CI = 0.54–1.25; I2 = 71%; p = 0.36), need for ventilation (RR = 0.49; 95%CI = 0.15–1.56; I2 = 71%; p = 0.57), and incidence of pneumothorax (RR = 1.24; 95%CI = 0.30–5.12; I2 = 0%; p = 0.77) in the CPAP group compared to the ETI group. Regarding secondary outcomes, compared to the ETI group, no significant differences were found in APGAR at one minute (MD = −1.01; 95%CI −2.97 to 0.94; I2 = 98%; p = 0.31), APGAR at 5 min (MD = −1.00; 95%CI = −2.96 to 0.95; I2 = 99%; p = 0.32), days of hospitalization (MD = −0.52; 95%CI = −1.46 to 0.42; I2 = 94%; p = 0.28), and cord pH (MD = 0.003; 95%CI = −0.01 to 0.02; I2 = 0%; p = 0.79). Conclusions: In patients with MAS, there is no significant effect of CPAP use compared to ETI on primary, specifically on mortality, need for ventilation, the incidence of pneumothorax, and secondary outcomes.