To examine how youth multiple tobacco product (MTP) users differ relative to non-users and to single-product users on risk factors at multiple levels of influence.We analyzed data on high school students from the North Carolina Youth Tobacco Survey, 2015 (n = 2922). Single- and MTP use were defined as use of one, or two or more tobacco products in the past month, respectively. Multinomial regressions estimated the association between risk factors and MTP use compared to single-product use and non-use of tobacco. Risk factors included intra-personal (e.g., harm perceptions), and interpersonal (e.g., household, peer tobacco use, secondhand smoke or vapor, and advertising) factors.Of students, 12% and 13% were single product and MTP users, respectively. Many differences emerged between MTP users and non-tobacco users, with MTP users showing lower harm perceptions, higher perceived social benefits of smoking, significantly higher relative risk of having friends who use tobacco (RRR = 4.79, 95% CI 3.42, 6.70), of exposure to secondhand e-cigarette vapor (RRR = 1.35, 95% CI 1.23, 1.48), and of being receptive to tobacco marketing (RRR = 4.01, 95% CI 2.87, 5.61). Fewer differences emerged between MTP and single product users with MTP users having significantly higher relative risk of having friends who use tobacco (RRR = 2.31 95% CI 1.73, 3.07), of exposure to secondhand vapor (RRR = 1.10, 95% CI 1.02, 1.18), and of being receptive to tobacco marketing (RRR = 1.71, 95% CI 1.17, 2.50).Efforts that target multiple tobacco product use should increase youth tobacco-related harm perceptions, and protect youth from social, peer, and industry influences.