Sevoflurane is associated with a relatively high incidence of emergence agitation (EA) in children. Prophylactic treatment, including midazolam, dexmedetomidine, ketamine, fentanyl and propofol, has been used to prevent EA. However, the question of which prophylactic treatment should be preferred to decrease the incidence of EA is still unclear. We conducted a network meta-analysis of randomized controlled trials to investigate the comparative efficacy of midazolam, dexmedetomidine, ketamine, fentanyl, and propofol for the prevention of sevoflurane-related EA in children. First, we used the odds ratios and 95% confidence interval as effect size. The results revealed that dexmedetomidine 0.19 (0.14–0.27), midazolam 0.22 (0.07–0.60), ketamine 0.28 (0.16–0.51), propofol 0.23 (0.10–0.53), and fentanyl 0.25 (0.17–0.36) led to a significant reduction of the incidence of EA when compared with placebo. With placebo as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω = 8.66728e-08). The logor were dexmedetomidine −1.75 (−2.11 to −1.39), midazolam −1.07 (−1.54 to −0.60), ketamine −1.292 (−1.92 to −0.66), and fentanyl −1.13 (−1.56 to −0.70). When compared with dexmedetomidine, the logor were placebo 1.75 (1.39–2.11), midazolam 0.67 (0.09–1.25), ketamine 0.45 (−0.25–1.15), propofol 0.75 (0.19–1.31), and fentanyl 0.617 (0.13–1.11). When compared with ketamine, the logor were placebo 1.29 (0.66–1.92), midazolam 0.22 (−0.56 to 1.00), dexmedetomidine −0.45 (−1.15–0.25); propofol 0.29 (−0.45–1.03); and fentanyl 0.16 (−0.59–0.92). The study that showed dexmedetomidine, midazolam, ketamine, propofol, and fentanyl could significantly decrease the incidence of EA when compared with placebo. One interesting finding of this network meta-analysis is that dexmedetomidine might be the best choice to prevent EA. However, there is weak evidence that dexmedetomidine is better than ketamine for the prevention of sevoflurane-related EA in children. As a result, more studies are needed to compare dexmedetomidine with ketamine.