This study examines the relative effectiveness of using gain- versus loss-framed messages to promote H1N1 vaccination among older adults, focusing on the moderating roles of perceived vaccine safety and efficacy. An experiment was conducted with older adults recruited from senior centers in the state of Maryland. Results show that older adults who perceived low vaccine efficacy developed greater intentions to receive the vaccine when presented with a loss-framed message (versus a gain-framed message). For those who perceived high vaccine efficacy, message framing did not make a difference in postexposure intentions. Evidence regarding the interaction between message framing and perceived vaccine safety is limited. Theoretical and practical implications of the findings are discussed.