To determine the effectiveness and safety of prophylactic phototherapy compared with conventional phototherapy for the prevention of neonatal jaundice. We included clinical trials comparing prophylactic phototherapy to conventional phototherapy to prevent jaundice in premature newborns. We searched Embase, MEDLINE, LILACS, Central, and others. The statistical analysis was performed in RevMan (Review Manager 5.3). Outcomes were analyzed according to the type of variable: risk difference (RD) and mean difference (MD). A random effects model was used due to heterogeneity. We reported results in forest plots. Risk of bias was evaluated, and a sensitivity analysis was made. 1127 articles were found, and six studies (2332 patients) were included in the meta-analysis. Five studies evaluated the need for exchange transfusion as the primary outcome RD -0.01, 95% CI [-0.05 to 0.03]. One study evaluated bilirubin encephalopathy RD -0.04, 95% CI [-0.09 to 0.00]. Five studies evaluated the duration of phototherapy, MD 38.47, 95% CI [1.28 to 55.67]. Four studies evaluated levels of bilirubin (MD -1.23, 95% CI [-2.25 to -0.21]. Two studies evaluated mortality, RD 0.01, 95% CI [-0.03 to 0.04]. As a conclusion, compared to conventional phototherapy, prophylactic phototherapy decreases the last measured level of bilirubin, as well as the probability of neurodevelopmental disturbances. However, it increases phototherapy duration.