This study examined perceived risk of harm from smoking or ST use in a U.S. nationally representative sample of high school seniors and examined its association with current smoking status. Data were derived from the Monitoring the Future project for 1999 through 2003 (n = 11,093). We used multiple logistic regression analysis to examine the association between comparative perceived risk of harm of smoking and ST use with current smoking status, while adjusting for sex, race, and perceived risk of harm from smoking. In 1999-2003, 74.0% of high school seniors perceived great risk of harm from smoking and 44.9% perceived great risk from using ST. Perceived risk varied by smoking intensity: 80.3% of non-smokers perceived great risk of harm from smoking, compared to 49.7% of students who smoked about one-half pack per day and 36.1% of pack-a-day smokers. Overall, 52.7% perceived equal risk of harm from using either product, 41.3% perceived greater risk from cigarettes, and 6.1% perceived a greater risk from using ST. Adjusting for sex and race, high school seniors who perceived that smoking conveyed a greater risk for harm than did using smokeless tobacco were significantly more likely to be smokers than were those who perceived equal risk from the products (odds ratio [OR] = 1.43; 95% confidence interval [CI] 1.29-1.60). Those who perceived that using smokeless tobacco was riskier than smoking were even more likely to be current smokers (OR = 2.43; 95% CI 1.96-3.01). Effective methods for communicating accurate health risks to young people are needed.