We sought to examine the relationship between perceived message effectiveness (PME) and actual message effectiveness (AME) in a 3-week randomized trial of vaping prevention advertisements. Participants were US adolescents (n = 1,514) recruited in 2021. We randomly assigned them to view The Real Cost vaping prevention ads or control videos online. Participants viewed three videos at Visit 1, again at Visits 2 and 3, and completed a survey at each visit that assessed AME (susceptibility to vaping) and two types of PME - effects perceptions (potential for behavioral impact) and message perceptions (potential for message processing). At Visit 4, AME was measured. Compared to control, The Real Cost ads led to improved AME (lower susceptibility to vaping at Visit 4, p < .001). This was anticipated by The Real Cost ads eliciting higher PME ratings (higher effects and message perceptions at Visit 1, both p < .001). Furthermore, PME (both effects and message perceptions) at Visit 1 predicted susceptibility to vaping at Visits 1, 2, 3, and 4 (all p < .001). Finally, effects perceptions fully mediated the impact of The Real Cost ads on susceptibility to vaping (β = -.30; p < .001), while message perceptions only partially mediated the effect (β = -.04; p = .001). Our findings indicate a relationship between PME and AME, especially effects perceptions, and suggest that PME may be useful in message pre-testing to select messages with greater behavior change potential.