Abstract Background Qualitative research suggests that a shared route of administration (i.e. via inhalation) for the common forms of both tobacco (i.e. cigarettes) and cannabis (i.e. joints) may contribute to their co-occurring use. Methods We used data on 43,093 U.S. adults who participated in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether cannabis use and abuse/dependence were associated with smoked (cigarettes, cigars, pipes) versus smokeless (snuff, chewed tobacco) forms of tobacco use, even after controlling for socio-demographic, psychiatric and substance-related covariates. Results Tobacco smoking was associated with a 3.3–4.5 times increased risk for cannabis use and abuse/dependence respectively. After covariate adjustment, importantly for nicotine dependence, smoking tobacco (but not smokeless tobacco) was still significantly associated with both cannabis use (multinomial odds-ratio (MOR) 1.99) and cannabis dependence (MOR 1.55). In contrast, use of smokeless tobacco was not significantly correlated with elevated rates of cannabis use (MOR 0.96) or abuse/dependence (MOR 1.04). Conclusions Route of administration may play an important role in the observed association between tobacco and cannabis use. This may represent a physiological adaptation of the aero-respiratory system and/or index social and cultural influences surrounding the use of smoked versus smokeless forms of tobacco.