The effectiveness of two new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine and bupivacaine-phenylephrine) was compared with that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. This study was a prospective, randomized, double-blind trial conducted in the emergency department of a large children's hospital. Participants were 180 children 1 year of age or older with a laceration 5 cm or less in length that required suturing. Pain felt during suturing was scored by suture technicians, research assistants, parents, and patients 5 years of age and older using a visual analogue scale (VAS). There was no statistical difference demonstrated between the effectiveness of prilocaine-phenylephrine and that of TAC for any of the observer groups. A statistically significant difference was seen among anesthetics when comparing VAS scores of research assistants (P = .002), suture technicians (P = .006), and parents (P = .03), but not when comparing VAS ratings of patients (P = .07). Based on Tukey's post hoc test, these statistically significant differences were between TAC and bupivacaine-phenylephrine. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.3 VAS units for each rater group. In conclusion, this study demonstrated the effectiveness and safety of prilocaine-phenylephrine and bupivacaine-phenylephrine. Prilocaine-phenylephrine statistically outperformed bupivacaine-phenylephrine and offers an effective alternative to TAC during laceration repair in children.