The purpose of the study was to compare 30-day prevalence of alcohol, tobacco, and other drug use among twelfth-grade students in Montana across a rural-urban continuum during 2000, 2002, and 2004. The methods include an analysis of the Montana Prevention Needs Assessment (N = 15,372) using multivariable logistic regression adjusting for risk factors, protective factors, and demographics variables. Findings revealed that adolescent substance use varies across the rural-urban continuum. Risk of cigarette, smokeless tobacco, and alcohol use increased in more rural counties while risk of marijuana, LSD, and any drug decreased in more rural counties. The specificity provided through use of such a classification scheme has important implications for designing effective drug-prevention programs across diverse settings. (Contains 3 tables and 2 figures.)