Abstract Introduction Little research has examined the spillover effects of tobacco communication campaigns, such as how anti-smoking ads affect vaping. Aims and Methods Participants were a national sample of 623 U.S. adolescents (ages 13–17 years) from a probability-based panel. In a between-subjects experiment, we randomly assigned adolescents to view one of four videos online: (1) a smoking prevention video ad from the Food and Drug Administration’s (FDA) The Real Cost campaign, (2) a neutral control video about smoking, (3) a vaping prevention video ad from The Real Cost campaign, or (4) a neutral control video about vaping. We present effect sizes as Cohen’s d, standardized mean differences, with 95% confidence intervals (CIs). Results Exposure to The Real Cost vaping prevention ads led to more negative attitudes toward vaping compared with control (d = 0.30, 95% CI: 0.07, 0.53), while exposure to The Real Cost smoking prevention ads did not affect smoking-related outcomes compared with control (p-values > .05). Turning to spillover effects, exposure to The Real Cost smoking prevention ads led to less susceptibility to vaping (d = −0.34, 95% CI: −0.56, −0.12), more negative attitudes toward vaping (d = 0.43, 95% CI: 0.20, 0.65) and higher perceived likelihood of harm from vaping (d = 0.26, 95% CI: 0.04, 0.48), compared with control. Exposure to The Real Cost vaping prevention ads did not affect smoking-related outcomes compared with control (p-values > .05). Conclusions This experiment found evidence of beneficial spillover effects of smoking prevention ads on vaping outcomes and found no detrimental effects of vaping prevention ads on smoking outcomes. Implications Little research has examined the spillover effects of tobacco communication campaigns, such as how anti-smoking ads affect vaping. Using a national sample of 623 U.S. adolescents, we found beneficial evidence of spillover effects of smoking prevention ads on vaping outcomes, which is promising since it suggests that smoking prevention campaigns may have the additional benefit of reducing both smoking and vaping among adolescents. Additionally, we found that vaping prevention campaigns did not elicit unintended consequences on smoking-related outcomes, an important finding given concerns that vaping prevention campaigns could drive youth to increase or switch to using combustible cigarettes instead of vaping.