Media can deliver health and safety messages promoting child health and injury prevention. This study examined the effects of message framing and parental mediation on children’s perceptions of fire-safety messages. Using a 2 × 3 randomized experimental design, this study considered both message framing (gain or loss) and parental mediation (no mediation/control, unscripted, or scripted) with 320 children who were 4 and 5 years of age. Children saw two messages (burn and smoke inhalation) embedded in a cartoon. Afterward, researchers assessed children’s recall, understanding, and perceptions of self-efficacy and social norms. Children were more likely to recall the safety messages if they were older (burn: adjusted odds ration [AOR] = 2.74 and smoke: AOR = 2.58), and could recall the smoke inhalation message if they had unscripted mediation (AOR = 3.16). Message understanding was poor, with only about 50% of children choosing a correct behavior in a similar scenario. For the burn message, correct understanding was associated with gain-framing and scripted mediation (AOR = 3.22 and 5.77, respectively). Only the scripted mediation group was significantly associated with an increase in perceived social norms (burn: coefficient =.37 and smoke: coefficient =.55; P <.001. Gain-framing was associated with increased odds of self-efficacy for both behaviors (burn: AOR = 1.77 and smoke: AOR = 1.77). Messages that show positive outcomes combined with scripted parental mediation appear most effective in communicating safety behaviors, but the overall effectiveness of video-based messages to teach children safety behaviors needs to be enhanced.