The objective of this analysis was to identify variables that predict the initiation of smoking among adolescents, and the development of susceptibility to smoking, over a 2-year period. We assessed variables that might predict later smoking among nonsmoking students in grades 7 and 9 and assessed their smoking status 2 years later, when they were in grades 9 and 11, thus receiving data from 4,130 students at two time points. Initiation of weekly smoking over the 2 years was associated with having a parent, sibling, or close friend who smokes; low school grades; higher levels of deviant behavior; susceptibility to smoking; use of smokeless tobacco; and for 7th graders, perception of higher levels of normative smoking. Susceptibility, defined as not being able to rule out the idea of smoking a year after the survey, was identified as a strong predictor of smoking and a valuable intermediary measure. We also assessed factors associated with the prediction of susceptibility 2 years post-test. Susceptibility to smoking was associated with deviant behavior, low grades, lower parental monitoring, relaxed parental attitude toward youth smoking, ease of access to tobacco, and lower exposure to anti-tobacco messages. This study provides support for the idea that susceptibility to smoking could be a useful outcome variable for tobacco research, as an intermediary to the initiation of smoking. In addition, evidence indicates that theoretically manipulable variables, including access to tobacco and exposure to anti-tobacco information, have the potential to influence susceptibility to smoking over a time.