Introduction: The Family Smoking Prevention and Tobacco Control Act requires new pictorial warnings for U.S. cigarette packs, but enactment has been delayed by tobacco industry lawsuits. Research can inform implementation of the pictorial warning requirement and identify ways to optimize their public health impact post-implementation. This study investigated the impact of warning label message framing on young smokers' motivation to quit, examining cessation selfefficacy, and perceived risks as moderators of message framing impact. Methods: Smokers ages 18-30 (n = 740) completed baseline measures and were randomized to view 4 images of cigarette packs with pictorial health warnings featuring gain-or loss-framed messages. Motivation to quit was assessed after participants viewed the pack images. Linear models accounting for repeated measures and adjusting for baseline covariates examined the impact of message framing and interactions with baseline self-efficacy to quit and perceived risks of smoking. Results: Loss-framed warnings prompted significantly greater motivation to quit among smokers with high self-efficacy compared with smokers with low self-efficacy. Among smokers with low self-efficacy, gain-framed messages were superior to loss-framed messages. Gain-framed warnings generated significantly greater motivation to quit among smokers with high perceived risks compared with smokers with low perceived risks. Among smokers with high perceived risks, gainframed messages were superior to loss-framed messages. Conclusions: A combination of pictorial warnings featuring risk-based (i.e., loss-framed) and efficacy-enhancing (i.e., gain-framed) information may promote better public health outcomes. Research is needed to investigate how strategically framed warning messages impact smokers' behaviors based on their pre-existing attitudes and beliefs in real-world settings.